Wednesday, January 9, 2013

Early Brain Inflammation in Lupus (SLE)

I previously reviewed a brain research imaging study of patients with systemic lupus erythematosis (SLE).  This study found evidence of disruption of brain connectivity markers even before any clinical brain symptoms.

SLE is a multi-organ disease known to produce significant neuropsychiatric symptoms.  These symptoms do not affect all patients with SLE as the brain effects are highly variable in this disorder.  Studying patients with early SLE without brain-related symptoms provides insight into the timing, course and prevalence of brain pathophysiology.

A second study from the University of Texas Health Sciences Center at San Antonio, School of Medicine, Research Imaging Institute lends support to the early effect of SLE on the brain.

In this study, 85 subjects with SLE underwent brain positron emission tomography (PET).  PET imaging is a sensitive tool to assess brain glucose metabolism and brain inflammation.

The key elements of the design of this study included:

  • Case identification: Newly diagnosed SLE (within 9 months of initial diagnosis) with SLE disease severity measured by the SLE Disease Activity Index (SLEDAI)
  • Clinical presentation: Potential subjects with stroke were eliminated, 19 of the remaining sample had neuropsychiatric symptoms (anxiety, depression, psychosis, mononeuropathy or headache symptoms) and 17 had abnormal white matter hyperintensities or atrophy on magnetic resonance imaging (MRI).
  • Imaging parameters: Fluoro-deoxy-glucose (FDG) PET imaging analysis by visual inspection and statistical analysis by SLEDIA severity scores
The key findings from the study included:
  • 36 of 85 subjects (42%) showed abnormal PET images (decreased glucose uptake) on visual ratings localized to the frontal and parietal brain cortex
  • Disease activity ratings correlated with white matter increases in FDG uptake in multiple brain regions including: frontal, parietal and occipital regions, subcortical temporal regions, limbic regions, cerebellar white matter and brain stem areas
  • Subjects with neuropsychiatric symptoms showed hypermetabolism in frontal regions and subcortical white matter regions most notably in the corpus callosum regions
  • Subjects without neuropsychiatric symptoms showed hypermetabolism that was limited to frontal lobe, anterior cingulate and corpus callosum regions
It is interesting that the study was able to identify specific brain regions (corpus callosum noted in figure to the right) of white matter inflammation in those with anxiety, depression and other neuropsychiatric symptoms.  This supports a specific regional effect of the SLE disease process on production of psychiatric symptoms commonly found in the disorder. 

The author note their study is the first study that demonstrates a "strong association between SLE disease activity and increased FDG uptake indicating inflammation of white matter of newly diagnosed SLE patients".  They argue that this finding suggest that primary brain pathology in SLE is inflammation targeting white matter vascular and microglial structures. 

This is an important study using brain imaging to better understand the mechanisms related to the neuropathology of SLE.  The study supports an early onset of brain inflammation in SLE, often before any neuropsychiatric symptoms.  

For interested readers the complete text article can be accessed by selecting the PMID link below.

Photo of eclectus parrot from the author's files. 

Ramage, A., Fox, P., Brey, R., Narayana, S., Cykowski, M., Naqibuddin, M., Sampedro, M., Holliday, S., Franklin, C., Wallace, D., Weisman, M., & Petri, M. (2011). Neuroimaging evidence of white matter inflammation in newly diagnosed systemic lupus erythematosus Arthritis & Rheumatism, 63 (10), 3048-3057 DOI: 10.1002/art.30458

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