Eslicarbazepine acetate as a replacement for levetiracetam in people with epilepsy developing behavioral adverse events.

BACKGROUND: Psychiatric and behavioral side effects (PBSEs) are a major cause of antiepileptic drug (AED) withdrawal. Levetiracetam (LEV) is a recognized first-line AED with good seizure outcomes but recognized with PBSEs. Eslicarbazepine (ESL) is considered to function similarly to an active metabolite of the commonly used carbamazepine (CBZ). Carbamazepine is used as psychotropic medication to assist in various psychiatric illnesses such as mood disorders, aggression, and anxiety. AIM: The aim was to evaluate the psychiatric profile of ESL in people who had LEV withdrawn due to PBSEs in routine clinical practice to see if ESL can be used as a possible alternative to LEV. METHODS: A retrospective observational review was conducted in two UK epilepsy centers looking at all cases exposed to ESL since its licensing in 2010. The ESL group was all patients with treatment-resistant epilepsy who developed intolerable PBSEs to LEV, subsequently trialed on ESL. The ESL group was matched to a group who tolerated LEV without intolerable PBSEs. Psychiatric disorders were identified from case notes. The Hamilton Depression Scale (HAM-D) was used to outcome change in mood. Clinical diagnoses of a mental disorder were compared between groups using the Fisher's exact test. Group differences in HAM-D scores were assessed using the independent samples t-test (alpha=0.05). RESULTS: The total number of people with active epilepsy in the two centers was 2142 of whom 46 had been exposed to ESL. Twenty-six had previous exposure to LEV and had intolerable PBSEs who were matched to a person tolerating LEV. There was no statistical differences in the two groups for mental disorders including mood as measured by HAM-D (Chi-square test: p=0.28). CONCLUSION: The ESL was well tolerated and did not produce significant PBSEs in those who had PBSEs with LEV leading to withdrawal of the drug. Though numbers were small, the findings suggest that ESL could be a treatment option in those who develop PBSEs with LEV and possibly other AEDs.

Brief Report: Proatherogenic Cytokine Microenvironment in the Aortic Adventitia of Patients With Rheumatoid Arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of developing cardiovascular disease (CVD) via mechanisms that have not yet been defined. Inflammatory pathways, in particular within the vascular adventitia, are implicated in the pathogenesis of primary CVD but could be amplified in RA at the local tissue level. The aim of this study was to examine the aortic adventitia of coronary artery disease (CAD) patients with or without RA to determine the cytokine profile contained therein. METHODS: Aortic adventitia and internal thoracic artery biopsy specimens obtained from 19 RA patients and 20 non-RA patients undergoing coronary artery bypass graft surgery were examined by immunohistochemistry. RESULTS: Interleukin-18 (IL-18), IL-33, and tumor necrosis factor (TNF) were expressed in aortic adventitia biopsy specimens from both groups, and expression of these cytokines was significantly higher in RA patients. In RA patients, IL-33 expression in endothelial cells correlated positively with the number of swollen joints, suggesting a link between the systemic disease state and the local vascular tissue microlesion. CONCLUSION: The presence of the proinflammatory cytokines IL-18, IL-33, and TNF may play a role in the inflammatory process within the adventitia that contributes to plaque formation and destabilization. In theory, the amplified expression of these cytokines may contribute to the known increased occurrence and severity of CAD in patients with RA.

Interleukin-33 Triggers B1 Cell Expansion and Its Release of Monocyte/Macrophage Chemoattractants and Growth Factors.

B1 B lymphocytes are natural IgM-producing cells primarily found in peritoneum and mucosal sites. They perform vital functions during the early defence against viral and bacterial infections. Murine B1 cells express IL-33 receptor complex on activation. IL-33 is a new addition to the IL-1 family with a strong role in Th2 immunity. B1 cells have been recognized to exacerbate contact sensitivity by producing IgM and IL-5 in response to interleukin-33. However, the exact response of IL-33/ST2 signalling in B1 cells is not completely understood. In this study, we report that murine B1 cells respond directly to IL-33 in a ST2-dependent manner. This interaction instigates B1b cell proliferation in a time-dependent manner in vivo. Furthermore, it also mediates monocyte/macrophage and granulocyte recruitment via B1 cell release of chemokines (MCP-1 and MIP-1 alpha). It was noted that upon stimulation, B1b cells additionally release an angiogenic inducer vascular endothelial growth factor and granulocyte-monocyte colony-stimulating factor (GM-CSF). Our findings suggest that these IL-33-mediated B1 cells might be able to play a vital role in the recruitment and growth of monocytes and granulocytes.