Decrease in cortical vein opacification predicts outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND: The pathophysiology of brain injury after aneurysmal subarachnoid hemorrhage (aSAH) remains incompletely understood. Cerebral venous flow patterns may be a marker of hemodynamic disruptions after aneurysm rupture. We hypothesized that a decrease in venous filling after aSAH would predict cerebral ischemia and poor outcome. OBJECTIVE: To examine the hypotheses that venous filling as measured by the cortical venous opacification score (COVES) would (1) decrease after aSAH and (2) that decreased COVES would be associated with higher rates of hydrocephalus, vasospasm, delayed cerebral iscemia (DCI), and poor functional evaluation at outcome. METHODS: In this retrospective observational cohort study of consecutive patients with aSAH admitted to our tertiary care center between 2016 and 2018, we measured the COVES at admission and at subsequent CT angiography (CTA). We collected clinical variables and compared hydrocephalus, vasospasm, DCI, and outcome at discharge in patients with decrease in COVES with patients with stable COVES. RESULTS: A total of 22 patients were included in the analysis. COVES decreased from first CTA to second CTA in 11 (50%) patients, by an average of 1.1 points (P=0.01). Patients whose COVES decreased between admission and follow-up imaging were more likely to develop DCI (58% vs 0%, P=0.03) and have a poor outcome at discharge (100% vs 55%, P=0.03) than patients who had no change in COVES. aSAH severity was not associated with initial COVES, and there was no association between change in COVES and development of hydrocephalus or vasospasm. CONCLUSIONS: Development of decreased venous filling on CTA is associated with poor outcome after aSAH. This association suggests that venous hemodynamics may be reflective of, or contribute to, the pathophysiological mechanisms of brain injury after aSAH. Larger prospective studies are necessary to substantiate our findings.

An analysis of quality of life (QOL) in patients with epilepsy and comorbid psychogenic nonepileptic seizures (PNES) after vagus nerve stimulation (VNS).

PURPOSE: Patients with epilepsy (PWE) may suffer from comorbid psychogenic nonepileptic seizures (PNES). The efficacy of vagus nerve stimulation (VNS) in the treatment of epilepsy and depression is established, however the impact on PNES is unknown. Since many patients with PNES have comorbid depression, we explored the impact on quality of life (QOL) that VNS has on PWE and PNES. METHODS: The video electroencephalogram (vEEG) of all patients who underwent VNS at our institution was reviewed. Patients diagnosed with both psychogenic seizures and epileptic seizures on their vEEG were included in this study. These patients were contacted, and given a QOLIE-31 survey to assess their quality of life after VNS. Patients also completed a separate survey created by our group to categorize the quartile of their improvement. Pre-operative psychiatric disease was retrospectively reviewed. RESULTS: From a period of 2001 to 2016, 518 patients underwent placement of VNS for drug resistant epilepsy (DRE) at our institution. In total, 16 patients were diagnosed with both epilepsy and PNES. 11/16 patients responded to our questionnaire and survey. 9 out of 11 patients felt that their epileptic seizures had improved after VNS, while 7 of the 11 patients felt that their psychogenic episodes had improved. 2(28.6%), 1 (14.3%), and 4 (57.1%) of participants said their PNES improved by 25-50%, 50-75%, and 75-100%, respectively. 3(27.3%), 3 (27.3%), 1 (9.1%), and 4 (36.4%) of the participants said their epileptic seizures improved by 0-25%, 25-50%, 50-75%, and 75-100%, respectively. The average overall score for quality of life for the study participants was found to be 51 (±8) out of 100. CONCLUSION: Patients with epilepsy and comorbid PNES may benefit from VNS. It is unclear whether the benefit is conferred strictly from decreased epileptic seizure burden. The possible effect on PNES may be related to the known effect of VNS on depression. Further studies are necessary to elucidate the role of VNS in the treatment of PNES and possibly other psychiatric disease.

Generation of a new transgenic mouse model for assessment of tau gene silencing therapies.

BACKGROUND: Targeting the expression of genes has emerged as a potentially viable therapeutic approach to human disease. In Alzheimer's disease, therapies that silence the expression of tau could be a viable strategy to slow disease progression. METHODS: We produced a novel strain of transgenic mice that could be used to assess the efficacy of gene knockdown therapies for human tau, in live mice. We designed a tetracycline-regulated transgene construct in which the cDNA for human tau was fused to ubiquitin and to luciferase to create a single fusion polyprotein, termed TUL. RESULTS: When expressed in brain, the TUL polyprotein was cleaved by ubiquitin-processing enzymes to release the luciferase as an independent protein, separating the half-life of luciferase from the long-lived tau protein. Treatment of bigenic tTA/TUL mice with doxycycline produced rapid declines in luciferase levels visualized by in vivo imaging and ex vivo enzyme measurement. CONCLUSIONS: This new mouse model can be used as a discovery tool in optimizing gene targeting therapeutics directed to reduce human tau mRNA levels.