Whole Blood Viscosity and Cerebral Blood Flow in Acute Ischemic Stroke.

Existing effective treatments for ischemic stroke restore blood supply to the ischemic region using thrombolysis or mechanical removal of clot. However, it is increasingly recognized that successful removal of occlusive thrombus from the large artery-recanalization, may not always be accompanied by successful restoration of blood flow to the downstream tissues-reperfusion. Ultimately, brain tissue survival depends on cerebral perfusion, and a functioning microcirculation. Because capillary diameter is often equal to or smaller than an erythrocyte, microcirculation is largely dependent on erythrocyte rheological (hemorheological) factors such as whole blood viscosity (WBV). Several studies in the past have demonstrated elevated WBV in stroke compared with healthy controls. Also, elevated WBV has shown to be an independent risk factor for stroke. Elevated WBV leads to endothelial dysfunction, decreases nitric oxide-dependent flow-mediated vasodilation, and promotes hemostatic alterations/thrombosis, all leading to microcirculation sludging. Compromised microcirculation further leads to decreased cerebral perfusion. Hence, modulating WBV through pharmacological agents might be beneficial to improve cerebral perfusion in stroke. This review discusses the effect of elevated WBV on endothelial function, hemostatic alterations, and thrombosis leading to reduced cerebral perfusion in stroke.

Predicting Modafinil-Treatment Response in Poststroke Fatigue Using Brain Morphometry and Functional Connectivity.

Background and Purpose- Poststroke fatigue affects a large proportion of stroke survivors and is associated with a poor quality of life. In a recent trial, modafinil was shown to be an effective agent in reducing poststroke fatigue; however, not all patients reported a significant decrease in fatigue with therapy. We sought to investigate clinical and radiological predictors of fatigue reduction with modafinil therapy in a stroke survivor cohort. Methods- Twenty-six participants with severe fatigue (multidimensional fatigue inventory-20 ≥60) underwent magnetic resonance imaging at baseline and during the last week of a 6-week treatment period of 200 mg modafinil taken daily. Resting-state functional magnetic resonance imaging and high-resolution structural imaging data were obtained, and functional connectivity and regional brain volumes within the fronto-striato-thalamic network were obtained. Linear regression analysis was used to identify predictors of modafinil-induced fatigue reduction. Results- Multiple regression analysis showed that baseline multidimensional fatigue inventory-20 score (ß=0.576, P=0.006) and functional connectivity between the dorsolateral prefrontal cortex and the caudate nucleus (ß=-0.424, P=0.008) were significant predictors of modafinil-associated decreases in poststroke fatigue (adjusted r2=0.52, area under the receiver operator characteristic curve=0.939). Conclusions- Fronto-striato-thalamic functional connectivity predicted modafinil response for poststroke fatigue. Fatigue in other neurological disease has been attributed to altered function of the fronto-striato-thalamic network and may indicate that poststroke fatigue has a similar mechanism to other neurological injury related fatigue. Self-reported fatigue in patients with normal fronto-striato-thalamic functional connectivity may have a different mechanism and require alternate therapeutic approaches. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: ACTRN12615000350527.

Short- and Long-Term Efficacy of Modafinil at Improving Quality of Life in Stroke Survivors: A Post Hoc Sub Study of the Modafinil in Debilitating Fatigue After Stroke Trial.

BACKGROUND: The phase-II modafinil in debilitating fatigue after stroke trial demonstrated that modafinil improves fatigue and quality of life in severely fatigued stroke survivors. For this study, we sought to examine the interaction between fatigue and quality of life after stroke and determine whether reducing fatigue resulted in improved quality of life. In addition, we followed up a subset of patients 12-months after the trial to assess the long-term outcomes of modafinil therapy. METHODS: We used linear regression to analyze interaction between baseline fatigue, as measured by the multidimensional fatigue inventory (MFI), and quality of life, as measured by the stroke-specific quality of life scale (SSQoL); and between changes in MFI and SSQoL during treatment. Patients also took part in semi-structured interviews and study assessments 12-months after trial completion to assess long-term patterns of modafinil use, safety and efficacy. RESULTS: MFI and SSQoL were significantly correlated at baseline (ß = -1.975 95% CI -3.082, -0.869, p < 0.001), as were changes in MFI and SSQoL during treatment (ß = -1.054 95% CI -1.556, -0.553, p < 0.001). 18 patients agreed to 12-month follow-up, of whom 5 had continued to use modafinil. Patients taking modafinil daily demonstrated sustained improvement of 33-38 points in MFI compared to baseline. Two adverse events were reported and there was no evidence of drug tolerance. CONCLUSION: Modafinil appears to be safe and, for at least some patients, effective long-term in fatigued stroke survivors. Alleviating fatigue has a significant relationship with improved quality of life. CLINICAL TRIAL REGISTRATION: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368268, unique-identifier: ACTRN12615000350527.

Finite element modeling of optic chiasmal compression.

BACKGROUND: The precise mechanism of bitemporal hemianopia is still not clear. Our study investigated the mechanism of bitemporal hemianopia by studying the biomechanics of chiasmal compression caused by a pituitary tumor growing below the optic chiasm. METHODS: Chiasmal compression and nerve fiber interaction in the chiasm were simulated numerically using finite element modeling software. Detailed mechanical strain distributions in the chiasm were obtained to help understand the mechanical behavior of the optic chiasm. Nerve fiber models were built to determine the relative difference in strain experienced by crossed and uncrossed nerve fibers. RESULTS: The central aspect of the chiasm always experienced higher strains than the peripheral aspect when the chiasm was loaded centrally from beneath. Strains in the nasal (crossed) nerve fibers were dramatically higher than in temporal (uncrossed) nerve fibers. CONCLUSIONS: The simulation results of the macroscopic chiasmal model are in agreement with the limited experimental results available, suggesting that the finite element method is an appropriate tool for analyzing chiasmal compression. Although the microscopic nerve fiber model was unvalidated because of lack of experimental data, it provided useful insights into a possible mechanism of bitemporal hemianopia. Specifically, it showed that the strain difference between crossed and uncrossed nerve fibers may account for the selective nerve damage, which gives rise to bitemporal hemianopia.