ABSTRACT
Clozapine is an atypical antipsychotic used in refractory schizophrenia and depression. Its use is often complicated by its vast side-effect profile including cardiovascular reactions, agranulocytosis, and seizures. Specifically, the cardiac complications of clozapine have been shown to predominantly cause myocarditis and pericarditis. In this case report, the case of a 58-year-old male being treated for treatment-resistant depression and schizophrenia who suffers from tachycardia is presented. He is treated empirically for orthostatic hypotension with IV fluids without much success. Further imaging and echocardiography demonstrated a pericardial effusion, a rare reaction (≤1 : 10000) that has only been documented in a handful of case reports. This anecdotal evidence highlights the significance of polyserositis/pericardial effusion in the context of clozapine-induced orthostatic hypotension resistant to rehydration. When starting a patient on clozapine, it is important to consider further workup and monitoring with laboratory baseline biomarkers and cardiac evaluation with symptomatic individuals. Upon immediate cessation of clozapine, the pericardial effusion should spontaneously resolve without complication and should not be rechallenged.
ABSTRACT
Tauopathies are neurodegenerative disorders characterized by abnormal intracellular aggregates of tau protein, and include Alzheimer's disease, corticobasal degeneration, frontotemporal dementia, and traumatic brain injury. Glutamate metabolism is altered in neurodegenerative disorders manifesting in higher or lower concentrations of glutamate, its transporters or receptors. Previously, glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) demonstrated that glutamate levels are reduced in regions of synapse loss in the hippocampus of a mouse model of late-stage tauopathy. We performed a longitudinal GluCEST imaging experiment paired with a cross-sectional study of histologic markers of tauopathy to determine whether (1) early GluCEST changes are associated with synapse loss before volume loss occurs in the hippocampus, and whether (2) subhippocampal dynamics in GluCEST are associated with histopathologic events related to glutamate alterations in tauopathy. Live imaging of the hippocampus in three serial slices was performed without exogenous contrast agents, and subregions were segmented based on a k-means cluster model. Subregions of the hippocampus were analyzed (cornu ammonis CA1, CA3, dentate gyrus DG, and ventricle) in order to associate local MRI-observable changes in glutamate with histological measures of glial cell proliferation (GFAP), synapse density (synaptophysin, VGlut1) and glutamate receptor (NMDA-NR1) levels. Early differences in GluCEST between healthy and tauopathy mice were measured in the CA1 and DG subregions (30% reduction, P ≤ 0.001). Synapse density was also significantly reduced in every subregion of the hippocampus in tauopathy mice by 6 months. Volume was not significantly reduced in any subregion until 13 months. Further, a gradient in glutamate levels was observed in vivo along hippocampal axes that became polarized as tauopathy progressed. Dynamics in hippocampal glutamate levels throughout lifetime were most closely correlated with combined changes in synaptophysin and GFAP, indicating that GluCEST imaging may be a surrogate marker of glutamate concentration in glial cells and at the synaptic level. © 2016 Wiley Periodicals, Inc.
