Cerebral hypoperfusion detected by SPECT in patients with systemic lupus erythematosus is related to clinical activity and cumulative tissue damage

Abstract

Cerebral single-photon emission computed tomography (SPECT) is a sensitive technique for the detection of central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). The objective was to determine whether a relationship exists between cerebral hypoperfusion as detected by cerebral SPECT, cumulative tissue damage and the clinical activity of SLE. Cerebral technetium-99m-L,L-ethyl cysteinate dimer (99mTc-ECD) SPECT was performed in two groups of patients: 10 women with SLE (Group A) who had no previous history of major neuropsychiatric (NPS) manifestations and no minor NPS symptoms in the last six months, and 57 unselected women with SLE (Group B). In the same week that SPECT was performed, the SLE disease activity index (SLEDAI), SLICC/ACR damage index, native anti-DNA antibodies (ELISA) and erythrocyte sedimentation rate (ESR) were determined. In Group A, cerebral SPECT showed moderate or severe hypoperfusion (abnormal SPECT) in five patients without NPS symptoms, unrelated to age (mean 24.8 versus 27.8 years) or disease duration (mean 6.8 versus 9 years). Patients with significant cerebral hypoperfusion had greater clinical disease activity (mean SLEDAI 13.6 versus 7.6) (SLEDAI> 7 in 5/5 versus 1/5; Fisher: 0.023; OR: 33; 95% CI: 2.3-469.8) and ESR (mean 43.6 versus 9.8; P < 0.05). In Group B, the mean age of the 57 unselected women with SLE was 37 years (SD 6.3) and the mean duration of the disease was 9.7 years (SD 6.3). Cerebral SPECT revealed normal perfusion or mild hypoperfusion (normal SPECT) in 30 patients (52.6%), and moderate or severe hypoperfusion in 27 (47.4%). Hypoperfusion was unrelated to age, duration of SLE or concentrations of anti-DNA antibodies and C3 and C4 fractions. Patients with significant cerebral hypoperfusion had more active clinical disease (mean SLEDAI 13.92; SD 8.44 versus 4.56; SD 4.15) (Mann-Whitney, P < 0.005), more cumulative tissue damage (mean SLICC 2.66; SD 2.84 versus 1.03; SD 1.51) (Mann-Whitney, P = 0.035), and higher ESR values (mean 28.7; SD 22.5 versus 17.7; SD 13.3) (Mann-Whitney, P = 0.023) than patients with normal SPECT studies. Significant cerebral hypoperfusion was related both to NPS manifestations present at the time of the study (17 of 27, 63% versus 3 of 30, 10%) (OR: 15.3) and cumulative manifestations (19 of 27, 70.4% versus 8 of 30, 26.7%) (OR: 6.5), whether mild (OR: 5.5) or severe (OR: 8.2). In conclusion, cerebral hypoperfusion detected by SPECT in patients with SLE is related to clinical activity (SLEDAI), cumulative tissue damage (SLICC) and concomitant or previous NPS manifestations.

Cognitive Dysfunction in Systemic Lupus Erythematosus: Prevalence and Correlates

“…After keeping the patient at rest in a quiet area, 740 MBq of bicisate dihydrochloride (NeuroliteR; Dupont, Germany) were intravenously administered. Sixty-four images of 20 s each were acquired, and image reconstruction was performed using slices parallel to the frontal-occipital axis [21]. Images were interpreted by two independent observers who, apart from SLE diagnosis, were unaware of patient data.…”

“…Cerebral perfusion could be a particularly sensitive marker in the evaluation of central nervous system involvement in SLE [20]. Data of a subset of 10 patients included in the present investigation have been reported elsewhere [21]. …”

Altered functional neuronal activity in neuropsychiatric lupus: A systematic review of the fMRI investigations

“…While evidence of cortical and subcortical neuropathology has been demonstrated in MRI studies using magnetization transfer imaging and fluid-attenuated inversion recovery (5,6), no clear association of these findings with clinical symptoms has emerged, that could be considered when making or evaluating treatment decisions. Likewise, limited insight into the patterns of cognitive deficit in patients with SLE has been provided with other imaging methods, such as magnetic resonance spectrometry (7), positron emission tomography (PET) (8,9), and single-photonemission computed tomography (SPECT) (10,11).…”

Neuroimmunopathology in a murine model of neuropsychiatric lupus

“…Approximately 40% of the NP-SLE manifestations develop before the onset of SLE or at the time of diagnosis and about 60% within the first year after diagnosis (van Dam, 1991). While a histologically normal brain with no specific pathognomonic brain lesions is a possible finding in NP-SLE, various abnormalities include hypoperfusion (Colamussi et al, 1995;Handa et al, 2003;Huang et al, 2002;Lopez-Longo et al, 2003) and regional metabolic abnormalities (Komatsu et al, 1999;Sibbitt and Sibbitt, 1993;Brooks et al, 1997;Volkow et al, 1988). Brain atrophy, however, is the most frequent observation on CT scans (Gonzalez-Scarano et al, 1979;Kaell et al, 1986;Miguel et al, 1994;Omdal et al, 1989;Ainiala et al, 2005;Waterloo et al, 1999) and is proposed to reflect widespread and progressive neuronal loss (Sibbitt and Sibbitt, 1993;Sibbitt et al, 1994).…”