An Iatrogenic Model of Brain Small-Vessel Disease: Post-Radiation Encephalopathy.

Rita Moretti,Paola Caruso

doi:10.3390/ijms21186506

Abstract

We studied 114 primitive cerebral neoplasia, that were surgically treated, and underwent radiotherapy (RT), and compared their results to those obtained by 190 patients diagnosed with subcortical vascular dementia (sVAD). Patients with any form of primitive cerebral neoplasia underwent whole-brain radiotherapy. All the tumor patients had regional field partial brain RT, which encompassed each tumor, with an average margin of 2.6 cm from the initial target tumor volume. We observed in our patients who have been exposed to a higher dose of RT (30–65 Gy) a cognitive and behavior decline similar to that observed in sVAD, with the frontal dysexecutive syndrome, apathy, and gait alterations, but with a more rapid onset and with an overwhelming effect. Multiple mechanisms are likely to be involved in radiation-induced cognitive impairment. The active site of RT brain damage is the white matter areas, particularly the internal capsule, basal ganglia, caudate, hippocampus, and subventricular zone. In all cases, radiation damage inside the brain mainly focuses on the cortical–subcortical frontal loops, which integrate and process the flow of information from the cortical areas, where executive functions are “elaborated” and prepared, towards the thalamus, subthalamus, and cerebellum, where they are continuously refined and executed. The active mechanisms that RT drives are similar to those observed in cerebral small vessel disease (SVD), leading to sVAD. The RT’s primary targets, outside the tumor mass, are the blood–brain barrier (BBB), the small vessels, and putative mechanisms that can be taken into account are oxidative stress and neuro-inflammation, strongly associated with the alteration of NMDA receptor subunit composition.

Highlights

Ions derived from electrons’ ejection from either atoms or molecules, secondary to different stresses such as high temperature, electrical discharges, or electromagnetic and nuclear radiation [1,2], are the basis for radiation.Radiation-induced brain injury is classified as acute, early delayed, and late-delayed reactions based on the timing of the onset of symptoms [3,4,5]
We studied 114 primitive cerebral neoplasia, that were surgically treated, and underwent radiotherapy (RT), and compared their results to those obtained by 190 patients diagnosed with subcortical vascular dementia
We observed in our patients who have been exposed to a higher dose of RT (30–65 Gy) a cognitive and behavior decline similar to that observed in subcortical vascular dementia (sVAD), with the frontal dysexecutive syndrome, apathy, and gait alterations, but with a more rapid onset and with an overwhelming effect

Summary

Introduction

Ions derived from electrons’ ejection from either atoms or molecules, secondary to different stresses such as high temperature, electrical discharges, or electromagnetic and nuclear radiation [1,2], are the basis for radiation.Radiation-induced brain injury is classified as acute, early delayed (subacute), and late-delayed reactions based on the timing of the onset of symptoms [3,4,5]. Acute injury, occurring 48 h to several weeks after the end of the radiotherapy cure, is characterized by general symptoms such as fatigue and sleepiness, drowsiness, and central symptoms such as memory loss and local, and not irreparable, demyelination. The definite injuries occur from six months up to several years after radiotherapy; the demyelination is overwhelming and irreversible and ends in white matter necrosis [6]. The late-onset radiotherapy (RT) damages are irreversible and often fatal, especially when patients undergo chemotherapy together with radiation, (whole-brain RT (usually 4000–4500 cGy) plus a focal tumor boost [7,8]; the potentiating effect of nitrosoureas, chemotherapy on the neurotoxic effect of RT [9,10]; with methotrexate [11], temozolomide [12], or rituximab [13]). There have been significant developments in understanding the pathophysiological mechanisms of radiotherapy-induced brain damage, limited information on the etiology of radiation-induced damage to healthy brain tissue is currently disposable

Methods

Results

Conclusion