Impact of depressive symptoms on adverse effects in people with epilepsy on antiseizure medication therapy.

OBJECTIVE: We studied the impact of depressive symptoms on adverse effects (AEs) in people with epilepsy (PWE) on antiseizure medication (ASM) therapy. An effect of depression on the AE burden has already been reported. We studied the correlation of various depressive symptoms with specific AEs to assess which AEs are especially prone to being confounded by particular depressive symptoms. METHODS: PWE filled in a variety of questionnaires including the "Neurological Disorder Depression Inventory for Epilepsy" (NDDI-E), "Emotional Thermometers 4" (ET4) and "Liverpool Adverse Events Profile" (LAEP). Depression was defined by a NDDI-E score > 13. Depressive symptoms consisted of NDDI-E and ET4 items. Discriminant analysis identified those AEs (=LAEP items) that were most highly influenced by depression. Logistic regression analysis yielded correlations of different depressive symptoms with specific AEs. RESULTS: We included 432 PWE. The strongest discriminators for depression were the LAEP items "Depression", "Nervousness/agitation," and "Tiredness". Out of all depressive symptoms "Everything I do is a struggle" most strongly correlated with total LAEP score (odds ratio [OR] = 3.1) and correlated with all but one LAEP item. Other depressive symptoms correlated to varying degrees with total LAEP and item scores. The number of ASMs, lack of seizure remission, and female gender correlated with high LAEP scores. SIGNIFICANCE: To the best of our knowledge, we are the first to show that various depressive symptoms correlate with specific LAEP items. This information can be helpful for quick evaluation of whether the reporting of different LAEP items may be confounded by particular depressive symptoms. This is relevant because changes in therapy may differ depending on if AEs are confounded by depressive symptoms. Simply reporting a particular depressive symptom may give a clue to whether specific AEs are confounded by depression. Our findings confirm the importance of screening for depression in all PWE. PLAIN LANGUAGE SUMMARY: In this study we measured depressive disorder and side effects caused by medication used to treat epilepsy with self-reported questionnaires in a cohort of people with epilepsy. We found depressive disorder to influence the perception of side effects that are caused by drugs used to treat epilepsy. This knowledge can help to identify if the reporting of side effects is influenced by depression. Treating depression may help to reduce side effects and may thus increase the tolerability of anti-epileptic medication. People who tolerate their medication are more likely to take it and are thus less likely to develop epileptic seizure.

Multiparametric Analysis Combining DSC-MR Perfusion and [18F]FET-PET is Superior to a Single Parameter Approach for Differentiation of Progressive Glioma from Radiation Necrosis.

PURPOSE: Perfusion-weighted (PWI) magnetic resonance imaging (MRI) and O­(2-[18F]fluoroethyl-)-l-tyrosine ([18F]FET) positron emission tomography (PET) are both useful for discrimination of progressive disease (PD) from radiation necrosis (RN) in patients with gliomas. Previous literature showed that the combined use of FET-PET and MRI-PWI is advantageous; hhowever the increased diagnostic performances were only modest compared to the use of a single modality. Hence, the goal of this study was to further explore the benefit of combining MRI-PWI and [18F]FET-PET for differentiation of PD from RN. Secondarily, we evaluated the usefulness of cerebral blood flow (CBF), mean transit time (MTT) and time to peak (TTP) as previous studies mainly examined cerebral blood volume (CBV). METHODS: In this single center study, we retrospectively identified patients with WHO grades II-IV gliomas with suspected tumor recurrence, presenting with ambiguous findings on structural MRI. For differentiation of PD from RN we used both MRI-PWI and [18F]FET-PET. Dynamic susceptibility contrast MRI-PWI provided normalized parameters derived from perfusion maps (r(relative)CBV, rCBF, rMTT, rTTP). Static [18F]FET-PET parameters including mean and maximum tumor to brain ratios (TBRmean, TBRmax) were calculated. Based on histopathology and radioclinical follow-up we diagnosed PD in 27 and RN in 10 cases. Using the receiver operating characteristic (ROC) analysis, area under the curve (AUC) values were calculated for single and multiparametric models. The performances of single and multiparametric approaches were assessed with analysis of variance and cross-validation. RESULTS: After application of inclusion and exclusion criteria, we included 37 patients in this study. Regarding the in-sample based approach, in single parameter analysis rTBRmean (AUC = 0.91, p < 0.001), rTBRmax (AUC = 0.89, p < 0.001), rTTP (AUC = 0.87, p < 0.001) and rCBVmean (AUC = 0.84, p < 0.001) were efficacious for discrimination of PD from RN. The rCBFmean and rMTT did not reach statistical significance. A classification model consisting of TBRmean, rCBVmean and rTTP achieved an AUC of 0.98 (p < 0.001), outperforming the use of rTBRmean alone, which was the single parametric approach with the highest AUC. Analysis of variance confirmed the superiority of the multiparametric approach over the single parameter one (p = 0.002). While cross-validation attributed the highest AUC value to the model consisting of TBRmean and rCBVmean, it also suggested that the addition of rTTP resulted in the highest accuracy. Overall, multiparametric models performed better than single parameter ones. CONCLUSION: A multiparametric MRI-PWI and [18F]FET-PET model consisting of TBRmean, rCBVmean and PWI rTTP significantly outperformed the use of rTBRmean alone, which was the best single parameter approach. Secondarily, we firstly report the potential usefulness of PWI rTTP for discrimination of PD from RN in patients with glioma; however, for validation of our findings the prospective studies with larger patient samples are necessary.

Ciprofloxacin-Resistant Pseudomonas aeruginosa Lung Abscess Complicating COVID-19 Treated with the Novel Oral Fluoroquinolone Delafloxacin.

PURPOSE: We report the development of a lung abscess caused by a ciprofloxacin-resistant Pseudomonas aeruginosa in a patient with COVID-19 on long-term corticosteroid therapy. Successful antimicrobial treatment included the novel oral fluoroquinolone delafloxacin suggesting an oral administration option for ciprofloxacin-resistant Pseudomonas aeruginosa lung abscess. Case Presentation. An 86-year-old male was admitted to the hospital with fever, dry cough, and fatigue. PCR testing from a nasopharyngeal swab confirmed SARS-CoV-2 infection. An initial CT scan of the chest showed COVID-19 typical peripheral ground-glass opacities of both lungs. The patient required supplemental oxygen, and anti-inflammatory treatment with corticosteroids was initiated. After four weeks of corticosteroid therapy, the follow-up CT scan of the chest suddenly showed a new cavernous formation in the right lower lung lobe. The patient's condition deteriorated requiring high-flow oxygen support. Consequently, the patient was transferred to the intensive care unit. Empiric therapy with intravenous piperacillin/tazobactam was started. Mycobacterial and fungal infections were excluded, while all sputum samples revealed cultural growth of P. aeruginosa. Antimicrobial susceptibility testing showed resistance to meropenem, imipenem, ciprofloxacin, gentamicin, and tobramycin. After two weeks of treatment with intravenous piperacillin/tazobactam, the clinical condition improved significantly, and supplemental oxygen could be stopped. Subsequently antimicrobial treatment was switched to oral delafloxacin facilitating an outpatient management. CONCLUSION: Our case demonstrates that long-term corticosteroid administration in severe COVID-19 can result in severe bacterial coinfections including P. aeruginosa lung abscess. To our knowledge, this is the first reported case of a P. aeruginosa lung abscess whose successful therapy included oral delafloxacin. This is important because real-life data for the novel drug delafloxacin are scarce, and fluoroquinolones are the only reliable oral treatment option for P. aeruginosa infection. Even more importantly, our case suggests an oral therapy option for P. aeruginosa lung abscess in case of resistance to ciprofloxacin, the most widely used fluoroquinolone in P. aeruginosa infection.