Background Observational studies have demonstrated improved outcomes in TBI patients receiving in-hospital betablockers. The aim of this study is to conduct a randomized controlled trial examining the effect of beta-blockers on outcomes in TBI patients. Methods Adult patients with severe TBI (intracranial AIS C 3) were included in the study. Hemodynamically stable patients at 24 h after injury were randomized to receive either 20 mg propranolol orally every 12 h up to 10 days or until discharge (BB?) or no propranolol (BB-). Outcomes of interest were in-hospital mortality and Glasgow Outcome Scale-Extended (GOS-E) score on discharge and at 6-month follow-up. Subgroup analysis including only isolated severe TBI (intracranial AIS C 3 with extracranial AIS B 2) was carried out. Poisson regression models were used. Results Two hundred nineteen randomized patients of whom 45% received BB were analyzed. There were no significant demographic or clinical differences between BB ? and BBcohorts. No significant difference in inhospital mortality (adj. IRR 0.6 [95% CI 0.3-1.4], p = 0.2) or long-term functional outcome was measured between the cohorts (p = 0.3). One hundred fifty-four patients suffered isolated severe TBI of whom 44% received BB. The BB ? group had significantly lower mortality relative to the BBgroup (18.6% vs. 4.4%, p = 0.012). On regression analysis, propranolol had a significant protective effect on in-hospital mortality (adj. IRR 0.32, p = 0.04) and functional outcome at 6-month follow-up (GOS-E C 5 adj. IRR 1.2, p = 0.02). Conclusion Propranolol decreases in-hospital mortality and improves long-term functional outcome in isolated severe TBI. This randomized trial speaks in favor of routine administration of beta-blocker therapy as part of a standardized neurointensive care protocol. Level of evidence Level II; therapeutic.

Graves' disease (GD) is an autoimmune condition with elevated thyroid hormone levels and symptoms suggesting an affected brain. These symptoms often resolve with treatment but, for some patients, GD results in a long period of reduced wellbeing. The overall aim of this thesis is to characterize the consequences of GD with a special focus on the brain. Three studies were conducted with data from questionnaires and clinical assessments of patients with GD in both the hyperthyroid and the euthyroid phase. Paper I was a longitudinal cohort study that assessed long-term treatment results 6 10 years after the onset of GD. Among 1186 included patients, the 774 who were initially treated with antithyroid drugs had a 40% chance of being euthyroid without thyroid medication at follow-up. One in four patients did not feel fully recovered. Paper II was a longitudinal case-control study designed to characterize affective and cognitive symptoms in 65 premenopausal women with newly diagnosed untreated GD. At onset of GD, the patients were significantly more affected with depression, anxiety, and mental fatigue compared to controls. At follow-up after 15 months, these symptoms remained in a significant proportion of patients. Patients with eye symptoms or a history of psychiatric conditions were more likely to be affected with brain-related symptoms. Paper III was a longitudinal case-control study of 65 premenopausal women with newly diagnosed untreated GD designed to investigate the effect of GD on hippocampal volumes. At onset of GD, hippocampus and amygdala volumes of the patients were smaller compared to controls. These brain structures became larger with treatment and, after 15 months, only the left amygdala remained smaller than in controls. At inclusion, there was an inverse correlation between thyroid-stimulating hormone receptor antibody (TRAb) and the volumes of both amygdalae and the right hippocampus. There were also inverse correlations between TRAb and free triiodothyronine recovery and the recovery of most of the four assessed brain volumes. GD is a condition where a minority of patients can hope for a long-lasting restored thyroid function. A large proportion of GD patients do not feel recovered after 8 years. Mental fatigue is an important concept for understanding the brain-derived symptoms in GD. In summary, the studies demonstrate that Graves' hyperthyroidism has unexpected long-term consequences for many patients, provide extensive new data on the serious and chronic nature of GD, and show for the first time that GD is accompanied by reversible brain changes.

No abstract

No abstract