Neuroplasticity in Neuro-oncology: Neuropsychological and neuroimaging correlates of brain tumors

Brain tumors are a rare disease, however the cost in term of unfavorable prognosis and impact on quality of life is very high. The complex treatment requested by a brain tumor (surgery and pharmacological therapy) may determine neurological and cognitive consequences, that need an immediate and precise intervention. For this reason, novel diagnostic methods that combine behavioral and imaging data are requested. This research work was aimed at investigating cognitive and imaging correlates of brain tumors and is built on different aims. The first goal was the definition of the neuropsychological profile of brain tumors. We specifically focused on cognitive deficits associated with the pathophysiology of the tumor. In other words, we investigated if brain tumors may cause a specific type of cognitive damage, based on the specific pathophysiological behavior in affecting the brain. To this end, an observational study was designed and the assessment of a cohort of brain tumor patients in the pre-operative stage was performed. By means of an extensive neuropsychological protocol, patients were evaluated in different cognitive domains. This study allows us to describe the cognitive features of the tumors, by taking into account some physiological variables: type of tumor (e.g. glioma vs meningioma), site of the lesion, extension of the lesion. To the best of our knowledge, no study so far has defined the cognitive profile of brain tumors taking in account the specific neurological nature of this pathology, in order to define a suitable neuropsychological battery for the cognitive characterization of brain tumors. The second aim concerned precisely the effort to define the specificity of the neuropsychological battery in detecting the particular cognitive disease consequent to brain tumors. To achieve this goal, we compared the neuropsychological performance of the group of patients with brain tumor with a group of patients with focal stroke, a neurological disorder involving a very different pathophysiological process. This implies the identification of the neuropsychological tests that are sensitive in detecting the specific as well as subtle cognitive deficits consequent to brain tumors. 7 The third aim had a longitudinal perspective and concerned the study of the effects of tumor resection on cognitive functions in the long term. To achieve this goal, we analyzed the behavioral data of the group of patients at three different time points: pre-surgical, post-surgical and one month follow-up. We expected a global worsening of the cognitive scores in the immediate post-operative stage, with a subsequent recovery at one month follow-up. A preliminary study was also conducted in order to define the effect of the treatment (radiotherapy and chemotherapy) on cognitive functions, with the aim to clarify the interaction of surgery and treatment in affecting the brain. Hence a further follow-up was also conducted four months from the neurosurgery and after the therapy. Importantly, this study clarified the interaction between the cognitive effects of the treatment and surgical intervention. Furthermore, it shed light on the relevance of follow-up neuropsychological assessment in monitoring brain tumors. The present doctoral thesis aimed at clarifying the contribution of neuropsychological as well as neuroimaging measures in order to better characterize the specific pathophysiological processes beneath functional and cognitive symptoms. For this reason, a further effort consisted in exploring structural and functional neuroimaging biomarkers able to predict the patient’s quality of life after tumor surgical resection. We furthermore aimed to assess the added value of the use of local and global brain connectivity in the clinical decision process. To this end, together with the neuropsychological evaluation, metabolism and perfusion data were longitudinally acquired, using simultaneous dynamic PET and MRI techniques. These data were acquired before surgery, after one month, and after three months from surgery. This study is still ongoing. The overarching goal in the long term of the whole research is to take into account together neuroplasticity and neuropsychological aspects in neuro-oncology in order to create a new way of taking care of patients with brain tumor. Of note, the correlation between tumor variables, behavioral outcome and structural, functional, and metabolic metrics of brain organization allows individualized planning of surgery and treatment. This planning will therefore be tailored considering the characteristics of the single patient, leading to a better outcome and a reduced impact on functions and quality of life.