Long-term cognitive dysfunction after radiation therapy for primary brain tumors.

Background: The extent of radiation therapy (RT)-induced changes in cognitive function is unknown. RT with protons instead of photons spares the healthy brain tissue more and is believed to reduce the risk of cognitive dysfunction. There is modest knowledge on which parts of the brain we need to spare, to prevent cognitive dysfunction. To uncover which cognitive domains is most affected, we compared cognitive functioning in brain tumor patients treated with neurosurgery and RT with brain tumor patients treated with neurosurgery alone. Methods: A cross-sectional study assessing cognitive function in 110 patients with a primary brain tumor grades I-III or medulloblastoma (grade IV) treated at Aarhus University Hospital (AUH), Denmark between 2006 and 2016. Two cohorts were established: a cohort of 81 brain tumor patients who had received neurosurgery followed by RT (RT+), and a cohort of 29 brain tumor patients who had only received neurosurgery (RT-). The patients underwent questionnaires and neuropsychological assessment with standardized tests. Results: Mean age was 53.5 years with an average time since diagnosis of 7.3 years. Compared with normative data, lower average scores were observed for the entire group on domains concerning of verbal learning and memory (p < .001), attention and working memory (p < .001), processing speed (p < .001), and executive functioning (p < .001). Compared to RT- patients, RT + patients scored lower on domains concerning processing speed (p = .04) and executive function (p = .05) and had higher impairment frequency on verbal fluency (p = .02) with 16% of patients exceeding 1.5 SD below normative data. Conclusions: Our results indicate that treatment, including RT, for a primary brain tumor may have negative long-term impact on cognitive function, especially on processing speed and executive function.

Cognitive impairment following radiation to hippocampus and other brain structures in adults with primary brain tumours.

BACKGROUND: Radiation therapy (RT) to the brain may result in cognitive impairment. The primary objective of the present study was to examine the relationship between RT dose to the hippocampus and learning and memory functions. Secondary objective was to examine relationships between doses to other brain structures and specific cognitive functions. METHODS: A cross-sectional analysis was undertaken in 78 primary brain tumour patients after RT. Cognitive function was assessed by neuropsychological tests. Test scores were standardized using normative data adjusted for age and level of education. Test-specific cognitive impairment was determined as a z-score ≤-1.5. Radiation dose to brain structures and test-specific cognitive impairment outcomes were fitted to a logistic regression model. RESULTS: High RT dose to the left hippocampus was associated with impaired verbal learning and memory (p = 0.04). RT dose to the left hippocampus, left temporal lobe, left frontal lobe and total frontal lobe were associated with verbal fluency impairment (p < 0.05) and doses to the thalamus and the left frontal lobe with impaired executive functioning (p ≤ 0.03). Finally, RT dose to the brain and thalamus were associated with impaired processing speed (p ≤ 0.05). CONCLUSION: The present study indicates that the hippocampus may be vulnerable to radiation and that high radiation doses to the left hippocampus may lead to significant verbal learning and memory impairment. High RT doses to the left hippocampus and other left side structures may result in impairments in verbal fluency, executive function, and processing speed. Validation of these findings are being undertaken in a prospective study.

Effect of ephedrine and phenylephrine on brain oxygenation and microcirculation in anaesthetised patients with cerebral tumours: study protocol for a randomised controlled trial.

INTRODUCTION: During brain tumour surgery, vasopressor drugs are commonly administered to increase mean arterial blood pressure with the aim of maintaining sufficient cerebral perfusion pressure. Studies of the commonly used vasopressors show that brain oxygen saturation is reduced after phenylephrine administration, but unaltered by ephedrine administration. These findings may be explained by different effects of phenylephrine and ephedrine on the cerebral microcirculation, in particular the capillary transit-time heterogeneity, which determines oxygen extraction efficacy. We hypothesised that phenylephrine is associated with an increase in capillary transit-time heterogeneity and a reduction in cerebral metabolic rate of oxygen compared with ephedrine. Using MRI and positron emission tomography (PET) as measurements in anaesthetised patients with brain tumours, this study will examine whether phenylephrine administration elevates capillary transit-time heterogeneity more than ephedrine, thereby reducing brain oxygenation. METHODS AND ANALYSIS: This is a double-blind, randomised clinical trial including 48 patients scheduled for surgical brain tumour removal. Prior to imaging and surgery, anaesthetised patients will be randomised to receive either phenylephrine or ephedrine infusion until mean arterial blood pressure increases to above 60 mm Hg or 20% above baseline. Twenty-four patients were allocated to MRI and another 24 patients to PET examination. MRI measurements include cerebral blood flow, capillary transit-time heterogeneity, cerebral blood volume, blood mean transit time, and calculated oxygen extraction fraction and cerebral metabolic rate of oxygen for negligible tissue oxygen extraction. PET measurements include cerebral metabolic rate of oxygen, cerebral blood flow and oxygen extraction fraction. Surgery is initiated after MRI/PET measurements and subdural intracranial pressure is measured. ETHICS AND DISSEMINATION: This study was approved by the Central Denmark Region Committee on Health Research Ethics (12 June 2015; 1-10-72-116-15). Results will be disseminated via peer-reviewed publication and presentation at international conferences. TRIAL REGISTRATION NUMBER: NCT02713087; Pre-results. 2015-001359-60; Pre-results.