Posterior reversible encephalopathy syndrome (PRES) refers to a clinical neuro-radiologic entity with characteristic features on neuro-imaging depicting posterior cerebral white matter edema. Clinical symptoms include headache, visual disturbances, confusion, and seizures. We report six cases of acute PRES who had eclampsia and presented with recurrent episodes of convulsions and hypertension. Magnetic resonance imaging scan showed diffuse abnormal signal intensities involving deep white matter of occipital region. Follow-up examination after 2 weeks of conservative management, showed marked improvement clinically and on neuro-imaging following which patients were discharged in stable condition.

No abstract

Background Patients with rheumatoid arthritis (RA) exhibit substantial variability in both the magnitude and duration of their clinical response to treatment. Despite considerable research, no biomarker has reproducibly been shown to predict likelihood of clinical response to biologic therapy. There remains significant unmet medical need to identify patients who will have a meaningful clinical response to treatment prior to drug exposure. We have recently demonstrated efficacy of BAFF blockade in RA using tabalumab (previously known as LY2127399)1. We have now used gene expression profiling of whole blood mRNA, obtained prior to drug exposure, to identify a predictive gene expression pattern that helps identify patients that are highly likely to respond to treatment with tabalumab. Methods Whole blood mRNA was obtained at baseline from 158 RA subjects with an inadequate response to methotrexate enrolled in a phase 2 randomized trial in which patientsreceived placebo, 1, 3, 10, 30, 60 or 120 mg of tabalumab every 4 weeks over 24 weeks. Clinical results of BAFF blockade in RA of this study have recently been reported1. In addition to the RA subjects (152 samples passed quality control), samples from 30 healthy blood donor controls were analyzed using Affymetrix U133 Plus 2.0 expression arrays to determine gene expression, and data were compared after normalization using Robust Multichip Average (RMA) algorithm3. Human C-type Lectin Domain Family 4, Member C (CLEC4C) qPCR was performed in validated assays at Covance Genomics Seattle using primers and probes obtained from ABI. Statistical analyses were performed using Messina2, two sample t-test or regression modeling. Results There was a bimodal distribution of CLEC4C mRNA in whole blood from RA patients and controls at baseline. The mean level of CLEC4C gene expression measured by Affymetrix was lower in patients than in controls. Mean expression after normalization for patients (n=152) is 5.79 with a range of 3.18 to 9.69. Mean expression for control healthy blood donors (n=30) is 6.88, range is 4.36 to 9.02. Among patients, those with higher levels of CLEC4C gene expression were more likely to respond to tabalumab (as measured by ACR-N). Messina analysis2 at baseline identified both CLEC4C probe sets as having the largest margin when comparing responder and non-responder group outcome at week 16 using ACR-N/DAS28. A two sample t-test on the same data was significant (p<0.0007). These expression findings from selected Affymetrix probe sets were validated using qPCR; for CLEC4C the change in threshold cycle versus ACR-N was statically significant after correction for multiple comparisons using False Discovery Rate (FDR) and Bonferroni techniques (FDR p=0.013, Bonferroni p=0.013). Conclusions The subgroup of RA patients with higher levels of CLEC4C mRNA expression at baseline was significantly more likely to respond to treatment with tabalumab. Independent replication of these hypothesis generating findings is now in progress in a large phase 3 clinical trial...