Quality of life and its association with comorbidities and adverse events from antiepileptic medications: Online survey of patients with epilepsy in Australia.

OBJECTIVE: This study aimed to explore the quality of life (QoL) of adult patients with epilepsy (PwE) in Australia and its relationship with comorbidities and adverse events (AEs) from antiepileptic drugs (AEDs). METHODS: Cross-sectional surveys were completed by PwE, or carer proxies, recruited via the online pharmacy application MedAdvisor and Australian PwE Facebook groups from May to August 2018. Data were collected on demographics, epilepsy severity and management, AEs, comorbidities, and QoL (using the Patient-Weighted Quality of Life in Epilepsy Inventory [QOLIE-10-P] total score). Two linear regression models were constructed to explore associations between AEs or comorbidities and QOLIE-10-P score, with possible confounders determined using stepwise selection. RESULTS: Nine hundred and seventy-eight of 1267 responses were eligible (mean age of respondents: 44.5 years, 64% female, 52% employed). Recent AED use was reported by 97%; 47% were on AED monotherapy, 35% had ≤2 lifetime AEDs, and 55% were seizure-free for >1 year. After stepwise selection, control variables included in both models were time since diagnosis, employment status, seizure frequency, number of currently prescribed AEDs, and number of general practitioner (GP) visits per year. In the model for comorbidities, "psychiatric disorders" was associated with the largest QOLIE-10-P score decrease (-23.14, p < 0.001). In the model for AEs, which additionally controlled for depression and anxiety disorder, self-reported "memory problems" was associated with the largest decrease in QOLIE-10-P score (-14.27, p < 0.001). CONCLUSIONS: In this survey of Australian PwE, many of whom had relatively well-controlled epilepsy, psychiatric and self-reported memory problems were common and associated with the greatest detrimental impact on QoL. Further research is needed to better understand the underlying causes of impaired QoL and thereby improve its management.

Prion Diseases.

Prion diseases are a group of invariably fatal and transmissible neurodegenerative disorders that are associated with the misfolding of the normal cellular prion protein, with the misfolded conformers constituting an infectious unit referred to as a "prion". Prions can spread within an affected organism by directly propagating this misfolding within and between cells and can transmit disease between animals of the same and different species. Prion diseases have a range of clinical phenotypes in humans and animals, with a principle determinant of this attributed to different conformations of the misfolded protein, referred to as prion strains. This chapter will describe the different clinical manifestations of prion diseases, the evidence that these diseases can be transmitted by an infectious protein and how the misfolding of this protein causes disease.

The prion protein preference of sporadic Creutzfeldt-Jakob disease subtypes.

Sporadic Creutzfeldt-Jakob disease (CJD) is the most prevalent manifestation of the transmissible spongiform encephalopathies or prion diseases affecting humans. The disease encompasses a spectrum of clinical phenotypes that have been correlated with molecular subtypes that are characterized by the molecular mass of the protease-resistant fragment of the disease-related conformation of the prion protein and a polymorphism at codon 129 of the gene encoding the prion protein. A cell-free assay of prion protein misfolding was used to investigate the ability of these sporadic CJD molecular subtypes to propagate using brain-derived sources of the cellular prion protein (PrP(C)). This study confirmed the presence of three distinct sporadic CJD molecular subtypes with PrP(C) substrate requirements that reflected their codon 129 associations in vivo. However, the ability of a sporadic CJD molecular subtype to use a specific PrP(C) substrate was not determined solely by codon 129 as the efficiency of prion propagation was also influenced by the composition of the brain tissue from which the PrP(C) substrate was sourced, thus indicating that nuances in PrP(C) or additional factors may determine sporadic CJD subtype. The results of this study will aid in the design of diagnostic assays that can detect prion disease across the diversity of sporadic CJD subtypes.

Gene knockout of tau expression does not contribute to the pathogenesis of prion disease.

Prion diseases or transmissible spongiform encephalopathies are a group of fatal and transmissible disorders affecting the central nervous system of humans and animals. The principal agent of prion disease transmission and pathogenesis is proposed to be an abnormal protease-resistant isoform of the normal cellular prion protein. The microtubule-associated protein tau is elevated in patients with Creutzfeldt-Jakob disease. To determine whether tau expression contributes to prion disease pathogenesis, tau knockout and control wild-type mice were infected with the M1000 strain of mouse-adapted human prions. Immunohistochemical analysis for total tau expression in prion-infected wild-type mice indicated tau aggregation in the cytoplasm of a subpopulation of neurons in regions associated with spongiform change. Western immunoblot analysis of brain homogenates revealed a decrease in total tau immunoreactivity and epitope-specific changes in tau phosphorylation. No significant difference in incubation period or other disease features were observed between tau knockout and wild-type mice with clinical prion disease. These results demonstrate that, in this model of prion disease, tau does not contribute to the pathogenesis of prion disease and that changes in the tau protein profile observed in mice with clinical prion disease occurs as a consequence of the prion-induced pathogenesis.