Twenty-two consecutive inpatients with CNS-SLE in Peking Union Medical College Hospital were enrolled in this study, and 21 patients with non–CNS-SLE who were hospitalized at the same time were randomly selected as controls. All patients fulfilled ≥4 of the 1997 American College of Rheumatology (ACR) revised criteria for SLE (13). Both a rheumatologist and a neurologist diagnosed patients as having CNS-SLE due to significant and unequivocal change in neurologic or psychiatric function, identified by history, physical examination, and laboratory or radiographic tests, and further proved by clinical course and response to treatment, as required by the ACR criteria for CNS-SLE (14, 15). For example, cognitive dysfunction was diagnosed if significant deficits in any or all of the following cognitive functions were observed in the patients: simple or complex attention, reasoning, executive skills (e.g., planning, organizing, sequencing), memory (e.g., learning, recall), visual-spatial processing, language (e.g., verbal fluency), and psychomotor speed. A neurologic event was excluded if ≥1 criteria were present: hypertension (diastolic blood pressure >120 mm Hg), hypoxia (PaO2 <50 mm Hg), uremia (blood urea nitrogen >35.5 mmoles/liter), serious electrolyte imbalance, or culture-proved CNS infection. In accordance with the modified ACR nomenclature and case definitions (15), these 22 patients with CNS-SLE were further subdivided into diffuse presentations (n = 18), which included cognitive dysfunction, severe depression, acute confusional state, aseptic meningitis, movement disorder, and epilepsy, and focal presentations (n = 4), which included cerebral infarction and cerebral hemorrhage. All patients with CNS-SLE and controls received corticosteroids and/or cyclophosphamide treatment. For patients with positive antiphospholipid antibody, low-molecular heparin was also added if not contraindicated. Consent to participate in the study was obtained from all patients or their family. The research was approved by the Hospital Ethics Committee. All patients underwent SPECT and MRI, and 16 patients with CNS-SLE with abnormal SPECT findings at enrollment repeated SPECT 1–2 months after treatment.
In addition to neurologic assessment, each patient was evaluated for other evidence of SLE disease activity using a modification of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores (16). Active disease was defined as a modified SLEDAI score ≥8 (CNS disturbance was excluded from the modified SLEDAI scores).
Single-photon–emission computed tomography.
All patients received an intravenous injection of 99mTc-ethylenedicysteinate dimer (99mTc-ECD) at a dose of 1,110 MBq (30 mCi), and the scan was initiated 20 minutes later. The SPECT camera (Helix-HR; Elscint, Haifa, Israel) was equipped with double rotating heads. The images were scanned with a 64 × 64–pixel matrix, without zoom, with 3° angles comprising 180° for each head for a total of 120 images, with a scanning time of 20 seconds per angle and a total time of 20 minutes. The images were fed into a computer and reconstructed by applying a recovery filter with a cut frequency of 0.25 and a threshold of 4 in the axial, sagital, and coronal views with a thickness of 0.9 cm, presented later on the screen for interpretation. The images were analyzed in a blinded manner by 2 independent experienced physicians of nuclear medicine who did not have access to any demographic or clinical data. The examination was considered normal when there was a symmetrical and homogeneous concentration of 99mTc-ECD in both cerebral hemispheres, and it was considered abnormal when there was asymmetry in the distribution of the 99mTc-ECD in the whole hemisphere or in some lobe and/or when there were focal areas of low tracer concentration.
Magnetic resonance imaging scan.
MRI was performed with a 1.5T MRI system (Philips Medical Systems, Best, The Netherlands). Conventional T1-weighted spin-echo imaging, fluid-attenuated inversion recovery (FLAIR)-weighted imaging, and dual (proton density and T2-weighted) imaging were performed on all patients. Images were also read in a blinded manner by 2 experienced neuroradiologists who did not have access to any clinical data. T1-weighted imaging was performed using a spin-echo sequence with an echo time of 20 msec, a repetition time of 600 msec, and a scanning time of 3 minutes and 8 seconds. Dual fast spin-echo imaging was performed using an echo time of 23/120 msec, a repetition time of 2,500 msec, an echo train length factor of 10, and a scanning time of 2 minutes and 35 seconds. FLAIR fast spin-echo imaging was performed using an echo time of 120 msec, a repetition time of 8,000 msec, an echo train length of 16, and a scanning time of 3 minutes and 28 seconds. All sequences consisted of 22 axial slices with a 6-mm thickness, a 222-mm2 field of view, a 0.6-mm interslice gap, and a 256 × 256–pixel matrix, with an 80% acquisition percentage.
The significance of the differences in the number of patients with positive baseline characteristics, laboratory findings, and SPECT and MRI abnormalities between study groups was determined using Fisher's exact test. The Statistical Package for the Social Sciences (SPSS) version 11.0 (SPSS, Chicago, IL) was used to analyze the data. In all tests, all probability values were 2-sided, and P values less than 0.05 were considered as significant difference.