Neuroimaging evidence of white matter inflammation in newly diagnosed systemic lupus erythematosus

Abstract

Objective Systemic lupus erythematosus (SLE) with central nervous system (CNS) involvement is frequent and can have high morbidity. The primary pathophysiology of SLE in the CNS is thought to be inflammation secondary to autoantibody-mediated vasculitis. Neuroimaging studies have reported hypometabolism (impending cell failure) and atrophy (late-stage pathology), but not inflammation. We used a validated index of SLE-related disease activity as a regressor for positron emission tomographic (PET) images of glucose uptake to detect the presence and regional distribution of inflammation (hypermetabolism) and tissue failure, apoptosis or atrophy (hypometabolism). Methods Eighty-five newly diagnosed SLE patients without focal neurological symptoms were studied. Disease activity was quantified using the SELENA SLE Disease Activity Index (SS). 18Fluoro-deoxy-glucose (FDG) PET images were analyzed by visual inspection and as group statistical parametric images using the SS score as the analysis regressor. Results SS-correlated increases in glucose uptake were found throughout the white matter, most marked in heavily myelinated tracts. SS-correlated decreases were found in frontal and parietal cortex, in a pattern similar to that seen by visual inspection and in prior reports of hypometabolism. Conclusion We interpret the SS-correlated increases in glucose consumption as potential evidence of inflammation, in keeping with prior reports of hypermetabolism in inflammatory disorders. To our knowledge, this is the first imaging evidence of SLE-induced CNS inflammation in an SLE inception cohort. The dissociation between 18FDG uptake characteristics, spatial distribution, and correlation with disease activity argues that glucose hyper- and hypometabolism reflect fundamentally different aspects of the pathophysiology of CNS SLE.

Neuroimaging of translocator protein in patients with systemic lupus erythematosus: a pilot study using [11C]DPA-713 positron emission tomography

“…Although regional hypermetabolism, an indirect indicator of neuroinflammation, was reported previously in a cohort of newly diagnosed SLE patients 1 , we did not observe SLE-mediated TSPO upregulation in this study, where all participating SLE patients were at least four years out from initial diagnosis. We cannot exclude the possibility that increased exposure to immune and disease-modifying medications over the longer duration of illness in our cohort may contribute to such observations.…”

“…One may seek to explain the lower cerebellar TSPO binding in cognitively normal SLE subjects by degradation of tissue and apoptosis, which were thought to be responsible for regional brain hypometabolism (abnormally low glucose utilization) observed in both early-stage and late-stage SLE cohorts in previous studies 1, 32, 34 . However, hypometabolism was found only in the frontal and parietal cortices, but not in the cerebellum.…”

Cognitive and White Matter Tract Differences in MS and Diffuse Neuropsychiatric Systemic Lupus Erythematosus

“…33,34 Numerous studies have also revealed WM abnormalities in patients with NPSLE, 35,36 including the presence of WM lesions 37 and increased WM tract diffusivity. 38 The pathogenesis of CNS involvement in SLE is likely related to an inflammatory response secondary to auto-antibody-mediated vasculitis.…”

“…38 The pathogenesis of CNS involvement in SLE is likely related to an inflammatory response secondary to auto-antibody-mediated vasculitis. 35 The increased sensitivity in DTI has proved useful for detecting WM tract deterioration.…”

2013 Update: Hopkins Lupus Cohort

“…This is encouraging for SLE patients and their physicians. Finally, brain positron emission tomography (PET) scans found CNS white matter inflammation in newly diagnosed SLE patients, indicating a possible mechanism of SLE cognitive impairment [32]. …”