When talking about decisionmaking for children with a life-threatening condition, the death of children with brain tumors deserves special attention. The last days of the lives of these children can be particularly harsh for bystanders, and raise questions about the suffering of these children themselves. In the Netherlands, these children are part of the group for whom a wide range of end-of-life decisions are discussed, and questions raised. What does the end-of-life for these children look like, and what motivates (...) physicians and parents to make decisions that may affect the life and death of these children? This article highlights the story of the parents of the sisters Roos and Noor. When both their daughters were diagnosed with a hereditary brain tumor, they had to make similar decisions twice. Their story sheds light on the suffering of children in the terminal phase, and how this suffering may motivate parents and physicians to make decisions that influence the end of life of these children’s lives.We argue that complete knowledge about suffering in the terminal phase of children with brain tumors is impossible. However, by collecting experiences like those of Roos and Noor, we can move toward an experienced-based understanding and better guide parents and physicians through these hardest of decisions. (shrink)

Brain tumor classification plays a niche role in medical prognosis and effective treatment process. We have proposed a combined feature and image-based classifier for brain tumor image classification in this study. Carious deep neural network and deep convolutional neural networks -based architectures are proposed for image classification, namely, actual image feature-based classifier, segmented image feature-based classifier, actual and segmented image feature-based classifier, actual image-based classifier, segmented image-based classifier, actual and segmented image-based classifier, and finally, CFIC. The (...) Kaggle Brain Tumor Detection 2020 dataset has been used to train and test the proposed classifiers. Among the various classifiers proposed, the CFIC performs better than all other proposed methods. The proposed CFIC method gives significantly better results in terms of sensitivity, specificity, and accuracy with 98.86, 97.14, and 98.97%, respectively, compared with the existing classification methods. (shrink)

This narrative symposium brings to light the extreme difficulties faced by parents of children diagnosed with brain tumors. NIB editorial staff and narrative symposium editors, Gigi McMillan and Christy A. Rentmeester, developed a call for stories that was distributed on several list serves and posted on Narrative Inquiry in Bioethics’ website. The call asks parents to share their personal experience of diagnosis, treatment, long–term effects of treatment, social issues and the doctor–patient–parent dynamic that develops during this process. Thirteen stories (...) are found in the print version of the journal and an additional six supplemental stories are published online only through Project MUSE. One change readers may notice is that the story authors are not listed in alphabetical order. The symposium editors had a vision for this issue that included leading readers through the timeline of this topic: diagnosis–treatment–acute recovery–recurrence–treatment (again)– acute recovery (again)– long-term quality of life– (possibly) end of life. Stories are arranged to help lead the reader through this timeline. Gigi McMillan is a patient and research subject advocate, co-founder of We Can, Pediatric Brain Tumor Network, as well as, the mother of a child who suffered from a pediatric brain tumor. She also authored the introduction for this symposium. Christy Rentmeester is an Associate Professor of Health Policy and Ethics in the Creighton University School of Medicine. She served as a commentator for this issue. Other commentators for this issue are Michael Barraza, a clinical psychologist and board member of We Can, Pediatric Brain Tumor Network ; Lisa Stern, a pediatrician who has diagnosed six children with brain tumors in her 20 years of practice; and Katie Rose, a pediatric brain tumor patient who shares her special insights about this world. (shrink)

Neuroimaging is critical in the diagnosis and treatment of brain cancers; however, the first detection of tumors is a challenge. Detection techniques like image segmentation are heavily reliant on the segmented image’s resolution. Magnetic resonance imaging tumor segmentation has emerged as a new study area in the medical imaging field. This spongy and delicate mass of tissue is the brain. Stable conditions allow for patterns to enter and interact with each other. To put it simply, a (...) class='Hi'>tumor is a mass of tissue that has grown unchecked by the natural mechanisms that keep it under control. When cells divide uncontrollably, they create a cancerous tumor. Brain tumors can be detected and segmented using a variety of methods. A new method for detecting brain tumors using MRI images is presented in this research. An innovative Woelfel filter is used for enhancement, and morphological segmentation approaches combined with anisotropic diffusion are used for segmentation. Segmentation of brain tumors can be accomplished using thresholding and morphological techniques, which are both effective. The tumor will be located and identified using morphological image processing. Image denoising refers to the process of removing artefacts such as noise and aliasing from digital images. Here MATLAB programming language is utilised as it incorporates all the toolboxes required for the application involved in the work. (shrink)

In Patricia Churchland's 2006 essay on free will, she cites the case of a middle-aged man who, without any prior history of misbehavior, suddenly became obsessed with child pornography and started to molest his 8-year-old stepdaughter. He was subsequently discovered to have a brain tumor affecting the frontal lobes, and when it is successfully treated his aberrant behavior stopped.Thomas Szasz is famous for his denunciation of the concept of mental illness, and his critique is partly responsible for instigating (...) an enduring philosophical discourse about the nature of mental disorder. Szasz's key insight was the recognition that we find it important to distinguish between situations that are characterized by... (shrink)

Two experiments tested the hypothesis that neurological abnormalities decrease punishment by decreasing perceptions of free will. Experiment 1 found that a brain tumor decreased punishment for criminal behavior by decreasing perceptions of the afflicted criminal’s free will. This effect was stronger for liberal and non-religious participants than for conservative and religious participants. Experiment 2 replicated Experiment 1 and additionally found that a brain tumor decreased perceptions of the afflicted criminal’s conscious decisions and true self, thereby decreasing (...) perceptions of his free will, thereby decreasing his punishment. Collectively, these results suggest that neurological abnormalities decrease punishment by decreasing perceptions of free will, especially among liberals and non-religious people. These results also suggest that neurological abnormalities decrease perceptions of free will – and ultimately decrease punishment – by decreasing perceptions of conscious decisions and the true self. (shrink)

Researchers have documented negative physical and emotional consequences for both family caregivers of persons with cancer as well as caregivers of persons with a neurologic disorder. However, there is a unique subset of caregivers who must provide care for someone who may suffer from both a short, terminal trajectory of disease, as well as neurological and neuropsychiatric sequelae — the caregiver of a person with a primary malignant brain tumor. The purpose of this article was to describe a (...) conceptual framework for providing care for a person with a primary malignant brain tumor. The demands of this particular care situation are described, as well as potential resources available to the caregiver to meet those demands. Finally, the stress response that results from the balance between care demands and caregiver resources is illustrated. Development of a conceptual framework for this caregiving population is the first step in assisting nurses to identify factors that place caregivers of persons with a primary malignant brain tumor at risk for negative consequences, and to design interventions to improve caregiver health. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:A Bittersweet Score:A Father’s Account of His Family’s 20-Year Journey After a Pediatric Brain Tumor DiagnosisChristopher RileyI hadn’t seen him for 20 years, not since the day he drilled a hole in Peter’s head and left the stainless steel drill and bloody bit on the bedside table. He figured prominently in the story I often told of that day when he, a doctor in training, [End Page (...) 3] informed my wife Kathy and me that, “Wow,” our five-year-old son had “an impressive tumor” in his brain. He announced it with the admiration I reserve for a touchdown pass or stunning sunset. Since that day, he had become a venerable physician. Back then he was the resident who met us in the ER after our pediatrician told us that the MRI of Peter’s brain was “not normal,” that “there might be a growth.” As if there might not be. I imagined that Peter’s brain might simply have an unusual shape, or that the scan revealed some undiscovered fracture and the authorities only wanted to lock me up and all with my son would be well. The thrilled young doctor slew those hopes with an ice pick: “Wow, that’s an impressive tumor.” I said, “That’s the first time anyone has used the word tumor.” The doctor appeared mortified and started over.Now 20 years later we found ourselves at the same party and I felt a compulsion to introduce myself, remind him we’d met that day in 1993, and tell him what had become of Peter and his family in the decades since he’d made that mortifying mistake, one I hoped had become for him a defining moment. To my disappointment, he didn’t seem to remember.Peter was my red-haired boy. Fearless and whip smart, he told a stream of knock-knock jokes and performed dance routines choreographed by his 8-year-old sister Rachel. Six months of headaches, vomiting and clumsy falls led to discovery of the tumor. When I phoned my parents with the news, I couldn’t speak the words, words that felt as if they spelled my boy’s doom. My body refused to pronounce them.The war for Peter’s life began with surgery. I sat with Kathy in the surgical waiting area, fearing every minute that I would see the surgeon approaching with his shoulders slumped in mortal defeat. I learned during those hours that fear of your child’s death is a physical pain, a constriction in the chest, a suffocation. At the end of that wait, the surgeon told us the tumor was out and Peter had survived. The pathology indicated the tumor was a medulloblastoma. Without additional treatment, including radiation, it was certain to come back. Kathy’s knees buckled. Having just endured one life-and-death battle, we were plunged into another. To complicate matters, Peter wasn’t waking from surgery. Even after the anesthesia wore off, Peter remained groggy, unable to move or focus his eyes.Through the following days, Peter failed to rouse or speak. Sores formed at the back of his neck where his unswallowed saliva pooled. Neurologists doubted he knew us. His doctors hoped Peter would recover but it was possible he would remain as he was indefinitely. As I sat holding his useless hand, watching his useless body, I thought I’d never loved him as much as I did now.Peter’s doctors presented two treatment options. The first consisted of relatively high doses of daily radiation, the most effective known method for preventing the return of the cancer. But radiation wasn’t good for young brains. It “shaved IQ points,” they said in wild understatement. So they offered a second, experimental option, one that reduced radiation by a third and added months of chemotherapy. The doctors hoped this new regimen would be as effective as the old but cause less cognitive damage. They asked us to choose. It seemed impossible. We gathered the scant available data. We weighed the risks. We prayed. We took a leap. Without asking him, we made a decision for Peter we knew... (shrink)

New targets for brain tumor therapies may be identified by mutations that cause hereditary microcephaly. Brain growth depends on the repeated proliferation of stem and progenitor cells. Microcephaly syndromes result from mutations that specifically impair the ability of brain progenitor or stem cells to proliferate, by inducing either premature differentiation or apoptosis. Brain tumors that derive from brain progenitor or stem cells may share many of the specific requirements of their cells of origin. These (...) tumors may therefore be susceptible to disruptions of the protein products of genes that are mutated in microcephaly. The potential for the products of microcephaly genes to be therapeutic targets in brain tumors are highlighted hereby reviewing research on EG5, KIF14, ASPM, CDK6, and ATR. Treatments that disrupt these proteins may open new avenues for brain tumor therapy that have increased efficacy and decreased toxicity. -/- . (shrink)

Objective: To investigate the differences between patients returning to work and those who did not after brain tumor surgery.Methods: Patients were evaluated before surgery and after 3 months. The Montreal Cognitive Assessment test, Trail-Making Test, 15-word Rey–Osterrieth Word List, F-A-S tests, and Karnosfky Performance Status were used to assess cognitive status, attention, executive functions, memory, word fluency, and functional status. Patient-reported outcome measures used to evaluate emotional distress and disability were the Hospital Anxiety and Depression Scale and World (...) Health Organization Disability Assessment Schedule. Clinical and work-related variables, PROMs, and cognitive tests were compared using chi-squared, t-test or Mann–Whitney U test.Results: Sixty patients were included. Patients returning to work were 61.3 and 31.0% among people with meningioma and glioma, respectively. They reported lower postoperative disability and lesser home-to-work travel time. Patients with meningioma also showed better preoperative and postoperative attention and executive functions, better postoperative functional and cognitive status, and lower frequency of treatments.Conclusions: These variables should be considered in a clinical context to plan interventions for people who need support during return to work and in future research to investigate preoperative and postoperative predictive factors of going back to work. (shrink)

This issue of Narrative Inquiry in Bioethics explores the concerns and point of view of parents who have had to confront the devastating diagnosis of a pediatric brain tumor. This commentary, written by a general pediatrician, is a synthesis of several narrative themes which touch on a range of topics from relapse to long-term sequelae and other issues that effect a growing population of pediatric brain tumor patients. It offers a glimpse into the problems that need (...) to be addressed by health professionals, educators and support teams who provide short and long term care to these patients and their families. (shrink)

Gene therapy approaches have great promise in the treatment of neurodegenerative disorders and malignant brain tumors. Neuwelt et al. review available viral-mediated gene therapy methods and their blood-brain-barrier (BBB) disruption delivery technique, briefly mentioning nonviral mediated gene therapy methods. This commentary discussed the BBB disruption delivery technique, viral and nonviral mediated gene therapy approaches to Parkinson's disease, and the potential use of antisense oligo to suppress malignant brain tumors.

This article explores three different comics by creators with brain tumors: _Rick_, written and drawn by Gordon Shaw; _Going Remote_, written by Adam Bessie and drawn by Peter Glanting; and _Parenthesis_, written and drawn by Élodie Durand. It examines how the affordances of the comics medium enables the creators to present an experience of subjective time that is multiple, diffuse, and contradictory, in contrast to the regular apportioning of time via calendars, schedules, and pathways essential to institutional neuro-oncology. The (...) question of time here is significant because the side effects of brain tumors can include blackouts, seizures, and periods of extreme fatigue, during which the experience of time can be significantly disrupted. The title of the article therefore evokes a temporal duality: on the one hand, it refers to the common phrase used to describe what clocks do, as well as our ability to read them; on the other hand, it speaks to one of the most important qualities of graphic medicine, which is that it allows patients dealing with medical or health issues to tell time differently. The article explores the representation of personal time in _Rick_, social time in _Going Remote_, and lost time in _Parenthesis_. (shrink)

In the case of magnetic resonance imaging (MRI) imaging, image processing is crucial. In the medical industry, MRI images are commonly used to analyze and diagnose tumor growth in the body. A number of successful brain tumor identification and classification procedures have been developed by various experts. Existing approaches face a number of obstacles, including detection time, accuracy, and tumor size. Early detection of brain tumors improves options for treatment and patient survival rates. Manually segmenting (...) brain tumors from a significant number of MRI data for brain tumor diagnosis is a tough and time-consuming task. Automatic image segmentation of brain tumors is required. The objective of this study is to evaluate the degree of accuracy and simplify the medical picture segmentation procedure used to identify the type of brain tumor from MRI results. Additionally, this work suggests a novel method for identifying brain malignancies utilizing the Bagging Ensemble with K-Nearest Neighbor (BKNN) in order to raise the KNN’s accuracy and quality rate. For image segmentation, a U-Net architecture is utilized first, followed by a bagging-based k-NN prediction algorithm for classification. The goal of employing U-Net is to improve the accuracy and uniformity of parameter distribution in the layers. Each decision tree is fitted on a little different training dataset during classification, and the bagged decision trees are effective since each tree has minor differences and generates slightly different skilled predictions. The overall classification accuracy was up to 97.7 percent, confirming the efficiency of the suggested strategy for distinguishing normal and pathological tissues from brain MR images; this is greater than the methods that are already in use. (shrink)

ObjectiveHopelessness and depression are strongly associated with suicidality. Given that physical and psychological outcomes can be altered with hope, hope is a therapeutic goal of increasing importance in the treatment of brain tumor patients. Moreover, it is not yet understood which factors affect the perception of hope in brain tumor patients. In addition, it remains uncertain whether lower-grade brain tumor patients suffer less from psycho-oncological distress than higher-grade brain tumor patients.MethodsNeuro-oncological patients were (...) examined perioperatively with the Distress Thermometer and the Herth Hope Index. In addition, psychological comorbidities and an assessment of general psycho-oncological distress were recorded.ResultsSixty-six brain tumor patients were included. No differences between higher- and lower-grade brain tumor patients were observed for general psycho-oncological distress and hope. However, higher-grade brain tumor patients showed a significantly higher level of depression and more negative expectations regarding therapeutic success. The extent of depression correlated negatively with hope.ConclusionUnexpectedly, higher-grade brain tumor patients remained as hopeful as lower-grade brain tumor patients despite the devastating diagnosis, higher levels of depression, and a worse expectation of therapeutic success. Conversely, lower-grade brain tumor patients experience as much psycho-oncological distress as patients with a higher-grade brain tumor, underpinning the imperative need for comprehensive psycho-oncological screening. For all brain tumor patients, considering hope is important to avoid suicides resulting from hopelessness and depression. (shrink)

Balancing self‐renewal and differentiation of stem cells is an important issue in stem cell and cancer biology. Recently, the Drosophila neuroblast (NB), neural stem cell has emerged as an excellent model for stem cell self‐renewal and tumorigenesis. It is of great interest to understand how defects in the asymmetric division of neural stem cells lead to tumor formation. Here, we review recent advances in asymmetric division and the self‐renewal control of Drosophila NBs. We summarize molecular mechanisms of asymmetric cell (...) division and discuss how the defects in asymmetric division lead to tumor formation. Gain‐of‐function or loss‐of‐function of various proteins in the asymmetric machinery can drive NB overgrowth and tumor formation. These proteins control either the asymmetric protein localization or mitotic spindle orientation of NBs. We also discuss other mechanisms of brain tumor suppression that are beyond the control of asymmetric division. (shrink)

Gliomas are diffuse and invasive brain tumors with the nefarious ability to evade even seemingly draconian treatment measures. Here we introduce a simple mathematical model for drug delivery of chemotherapeutic agents to treat such a tumor. The model predicts that heterogeneity in drug delivery related to variability in vascular density throughout the brain results in an apparent tumor reduction based on imaging studies despite continual spread beyond the resolution of the imaging modality. We discuss a clinical (...) example for which the model-predicted scenario is relevant. The analysis and results suggest an explanation for the clinical problem of the long-standing confounding observation of shrinkage of the lesion in certain areas of the brain with continued growth in other areas. (shrink)

PurposeAlthough an increasing body of literature suggests a relationship between brain irradiation and deterioration of neurocognitive function, it remains as the standard therapeutic and prophylactic modality in patients with brain tumors. This review was aimed to abstract and evaluate the prediction models for radiation-induced neurocognitive decline in patients with primary or secondary brain tumors.MethodsMEDLINE was searched on October 31, 2021 for publications containing relevant truncation and MeSH terms related to “radiotherapy,” “brain,” “prediction model,” and “neurocognitive impairments.” (...) Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool.ResultsOf 3,580 studies reviewed, 23 prediction models were identified. Age, tumor location, education level, baseline neurocognitive score, and radiation dose to the hippocampus were the most common predictors in the models. The Hopkins verbal learning and the trail making tests were the most frequent outcome assessment tools. All studies used regression as machine learning method. All models were judged to have a high risk of bias mainly due to issues in the analysis.ConclusionExisting models have limited quality and are at high risk of bias. Following recommendations are outlined in this review to improve future models: developing cognitive assessment instruments taking into account the peculiar traits of the different brain tumors and radiation modalities; adherence to model development and validation guidelines; careful choice of candidate predictors according to the literature and domain expert consensus; and considering radiation dose to brain substructures as they can provide important information on specific neurocognitive impairments. (shrink)

Background: Maximum safe resection of infiltrative brain tumors in eloquent area is the primary objective in surgical neuro-oncology. This goal can be achieved with direct electrical stimulation to perform a functional mapping of the brain in patients awake intraoperatively. When awake surgery is not possible, we propose a pipeline procedure that combines advanced techniques aiming at performing a dissection that respects the anatomo-functional connectivity of the peritumoral region. This procedure can benefit from intraoperative monitoring with computerized tomography scan (...) and brain shift correction. Associated with this intraoperative monitoring, the additional value of preoperative investigation combining brain mapping by navigated transcranial magnetic stimulation with various neuroimaging modalities has not yet been reported.Case Report: A 42-year-old left-handed man had increased intracranial pressure, left hand muscle deficit, and dysarthria, related to an infiltrative tumor of the right frontal lobe with large mass effect and circumscribed contrast enhancement in motor and premotor cortical areas. Spectroscopy profile and intratumoral calcifications on CT-scan suggested an WHO grade III glioma, later confirmed by histology. The aforementioned surgical procedure was considered, since standard awake surgery was not appropriate for this patient. In preoperative time, nTMS mapping of motor function was performed, combined with magnetic resonance imaging -based tractography reconstruction of 6 neural tracts and resting-state functional MRI connectivity of sensorimotor and language networks. In intraoperative time, DES mapping was performed with motor evoked response recording and tumor resection was optimized using non-rigid image transformation of the preoperative data to iCT data. Image guidance was updated with correction for brain shift and tissue deformation using biomechanical modeling taking into account brain elastic properties. This correction was done at crucial surgical steps, i.e., when tumor bulged through the craniotomy after dura mater opening and when approaching the presumed eloquent brain regions. This procedure allowed a total resection of the tumor region with contrast enhancement as well as a complete regression of IICP and dysarthria. Hand paresis remained stable with no additional deficit. Postoperative nTMS mapping confirmed the good functional outcome.Conclusion: This case report and technical note highlights the value of preoperative functional evaluation by nTMS updated intraoperatively with correction of brain deformation by iCT. This multimodal approach may become the optimized technique of reference for patients with brain tumors in eloquent areas that are unsuitable for awake brain surgery. (shrink)

Survivors of childhood brain tumors face many obstacles to living independently as adults. Causes for lack of independence are multifactorial and generally are investigated in terms of physical, cognitive, and psychosocial treatment–related sequelae. Little is known, however, about the role of expectation for survivors’ function. From a mixed–methods study including qualitative interviews and quantitative measures from 40 caregiver–survivor dyads, we compared the data within and across dyads, identifying four distinct narrative profiles: (A) convergent expectations about an optimistic future, (B) (...) convergent expectations about a less optimistic future, (C) non–convergent expectations about a less optimistic future, and (D) non–convergent expectations about an unclear future. Dyads both do well and/or struggle in systematically different manners in each profile. These profiles may inform the design of interventions to be tested in future research and help clinicians to assist families in defining, (re–)negotiating, and reaching their expectations of function and independence. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The Road to Understanding and Acceptance of the Late Effects of Pediatric Brain Tumors and TreatmentJeanne CarlsonWe had little warning or time to adjust to our daughter’s diagnosis. A call from her third grade teacher reporting that Sarah seemed to be having vision problems rapidly led to eye exams, an MRI, and the discovery of a Germinoma brain tumor in the suprastellar region of Sarah’s (...) class='Hi'>brain. We were terrified but began treatment feeling optimistic about the outlook for Sarah’s recovery. Luckily, Sarah’s treatment was relatively non–invasive and quick, chemotherapy and radiation, five months start to finish. We were thrilled to have Sarah’s treatment behind us.As any parent of a child with a life–threatening illness knows, family life is seriously disrupted by the countless doctor, lab, and hospital visits, the worry, and the financial strain that are suddenly added to the demands of everyday life. We did our best to balance our focus on both of our children as Sarah is a twin and we didn’t want her brother Will to suffer as a result of his sister’s illness. It wasn’t easy but we found a way to schedule Will’s usual play dates, baseball practice, and family time. We were all happy and relieved when Sarah’s treatment was completed, yet we would later learn that we had been incredibly naïve in two ways; we thought that our brain tumor journey was over after Sarah’s treatment was completed and we thought that we’d brought Will through the process without effect. We had a lot to learn.At the time of diagnosis we knew that Sarah’s memory and ability to express emotion had already been impacted by the tumor but we didn’t yet know what that would mean to her quality of life. We were virtually unaware however that at age nine the chemotherapy and radiation treatments that Sarah received would result in profound late effects. Following treatment Sarah successfully completed 3rd grade and even received excellent STAR test scores (California state standardized tests). In 4th grade however, Sarah’s performance began to diverge from that of her peers and she found herself struggling in school and unable to make friends. We began looking for ways to help our daughter.What followed was a five year long journey through testing, evaluations, individualized education plans (IEPs), and therapies, which, in the end, left our family needing to accept the fact that although Sarah remains intelligent and artistically talented, she suffers from a constellation of late effects that will always affect her ability to function in the world. As a result of Sarah’s tumor and treatment she struggles with Auditory Processing Disorder, word finding problems, poor executive function, inability to recognize how she feels, significant difficulty making decisions, inability to read social cues, poor memory, slow processing, an emotional age of about nine, and lots of anxiety. She is also panhypopituitary, meaning that she has no remaining pituitary function and must take replacement medications by pill and injection, has hypothalamic obesity (HO), which is primarily controlled by more medication, and Raynaud’s Disease. The HO is an ongoing challenge because if Sarah does gain weight she can’t lose it again and exercise is not an easy solution because, like many pediatric brain tumor survivors, Sarah is easily fatigued. Finally, although Sarah’s vision improved after treatment her vision loss is significant enough to prevent her from driving. We pieced together this understanding of Sarah’s challenges and disabilities slowly so it wasn’t until the end of our children’s middle school years that we finally accepted the magnitude of the damage caused by the tumor and treatment. Thereafter we changed our focus from what Sarah might achieve in life to how to support [End Page 21] her in the activities at which she still excels and how to keep her active, interested in life, and feeling good about herself.It would have been a huge gift if we had been provided with information about the possible late effects that can result from treating the brain of a 9–year–old... (shrink)

Background: The risk of surgery in eloquent areas is related to neuropsychological dysfunctions. Maximizing the extent of resection increases the overall survival. The onco-functional balance is mandatory when surgery involves cognitive areas, and maximal information on the cognitive status of patients during awake surgery is needed. This can be achieved using direct cortical stimulation mapping and, in addition to this, a neuropsychological monitoring technique called real-time neuropsychological testing. The RTNT includes testing protocols based on the area where the surgery is (...) performed. We reported on tests used for left temporal lobe surgery and our RTNT decision tree.Case Report: We reported our RTNT experience with a 25-year-old right-handed man with 13 years of schooling. He reported daily partial seizures. MRI revealed the presence of a low-grade glioma involving the temporo-insular cortex. The neuropsychological status presurgery which was within the normal range was combined with functional magnetic resonance imaging and diffusion tensor imaging information. Awake surgery plus RTNT was performed. Direct electrical stimulation during object naming elicited a motor speech arrest. Resection was continuously accompanied by the RTNT. The RTNT provided enriched information to the surgeon. Performance never dropped. A slight decrement in accuracy emerged for pseudoword repetition, short-term memory and working memory, phonological processing, and verbal comprehension. Total resection was performed, and the histological examination confirmed the nature of the lesion. Immediate postsurgery performance was within the normal range as it was the fMRI and DTI assessment.Conclusion: The RTNT provides essential information that can be used online, during surgery, for clinical aims to provide the surgeon with useful feedback on the cognitive status of patients. (shrink)

High-resolution neuroimaging modalities are used often in studies involving healthy volunteers. Subsequently, a significant increase in the incidental discovery of asymptomatic intracranial abnormalities raised the important ethical issues of when follow-up and treatment may be necessary. We examined the literature to establish a practical set of criteria for approaching incidental findings. Our objective is to develop an algorithm for when follow-up may be important and to provide recommendations that would increase the likelihood of follow-up. A systematic literature search was performed (...) using the PubMed and MEDLINE databases to identify articles describing brain tumors and intracranial aneurysms. The treatment algorithm we present suggests that incidental intracranial masses suspicious for glioma should be biopsied or resected, while other masses are to be followed with serial imaging based on the expected growth pattern. Lack of follow-up can result in adverse outcomes that can be mitigated by using technology to facilitate communication and improve follow-up care. The importance of training physicians to be good communicators is also stressed. New technology including automated telephone systems, texting and email will improve access to patients and hopefully encourage compliance and follow-up. (shrink)

Preoperative diagnosis of gastric cancer and primary gastric lymphoma is challenging and has important clinical significance. Inspired by the inductive reasoning learning of the human brain, transfer learning can improve diagnosis performance of target task by utilizing the knowledge learned from the other domains (source domain). However, most studies focus on single-source transfer learning and may lead to model performance degradation when a large domain shift exists between the single-source domain and target domain. By simulating the multi-modal information learning (...) and transfer mechanism of human brain, this study designed a multisource transfer learning feature extraction and classification framework, which can enhance the prediction performance of the target model by using multisource medical data (domain). First, this manuscript designs a feature extraction network that takes the maximum mean difference based on the Wasserstein distance as an adaptive measure of probability distribution and extracts the domain-specific invariant representations between source and target domain data. Then, aiming at the random generation of parameters bringing uncertainties to prediction accuracy and generalization ability of extreme learning machine network, the 1-norm regularization is used to implement sparse constraints of the output weight matrix and improve the robustness of the model. Finally, some experiments are carried out on the data of two medical centers. The experimental results show that the area under curves (AUCs) of the method are 0.958 and 0.929 in the two validation cohorts, respectively. The method in this manuscript can provide doctors with a better diagnostic reference, which has certain practical significance. (shrink)

In this paper an Artificial Neural Network (ANN) model, for predicting the category of a tumor was developed and tested. Taking patients’ tests, a number of information gained that influence the classification of the tumor. Such information as age, sex, histologic-type, degree-of-diffe, status of bone, bone-marrow, lung, pleura, peritoneum, liver, brain, skin, neck, supraclavicular, axillar, mediastinum, and abdominal. They were used as input variables for the ANN model. A model based on the Multilayer Perceptron Topology was established (...) and trained using data set which its title is “primary tumor” and was obtained from the University Medical Centre, Institute of Oncology, Ljubljana, Yugoslavia Test data evaluation shows that the ANN model is able to correctly predict the tumor category with 76.67 % accuracy. (shrink)

The aim of this article is to show how a tumor can modify energy substrates fluxes in the brain to support its own growth. To address this question we use a modeling approach to explain brain nutrient kinetics. In particular we set up a system of 17 equations for oxygen, lactate, glucose concentrations and cells number in the brain. We prove the existence and uniqueness of nonnegative solutions and give bounds on the solutions. We also provide (...) numerical simulations. (shrink)

A brain tumor is an abnormal mass or growth of a cell that leads to certain death, and this is still a challenging task in clinical practice. Early and correct diagnosis of this type of cancer is very important for the treatment process. For this reason, this study aimed to develop computer-aided systems for the diagnosis of brain tumors. In this research, we proposed three different end-to-end deep learning approaches for analyzing effects of local and deep features (...) for brain MRI images anomaly detection. The first proposed system is Directional Bit-Planes Deep Autoencoder which extracts and learns local and direction features. The DBP-DAE by decomposition of a local binary pattern into eight bit-planes extracts are directional and inherent local-structure features from the input image and learns robust feature for classification purposes. The second one is a Dilated Separable Residual Convolutional Network which extracts high and low-level features. The main advantage of this approach is that it is robust and shows stable results regardless to size of image database and to solve overfitting problems. To explore the effects of mixture of local and deep extracted feature on accuracy of classification of brain anomaly, a multibranch convolutional neural network approach is proposed. This approach is designed according to combination of DBP-DAE and DSRCN in an end-to-end manner. Extensive experiments conducted based on brain tumor in MRI image public access databases and achieves significant results compared to state-of-the-art algorithms. In addition, we discussed the effectiveness and applicability of CNNs with a variety of different features and architectures for brain abnormalities such as Alzheimer’s. (shrink)

Gliomas can display marked changes in the concentrations of energy metabolism molecules such as creatine (Cr), phosphocreatine (PCr) and lactate, as measured using magnetic resonance spectroscopy (MRS). Moreover, the BOLD (blood oxygen level dependent) contrast enhancement in functional magnetic resonance imaging (fMRI) can be reduced or missing within or near gliomas, while neural activity is not significantly reduced (so-called neurovascular decoupling), so that the location of functionally eloquent areas using fMRI can be erroneous. In this paper, we adapt a previously (...) developed model of the coupling between neural activation, energy metabolism and hemodynamics, by including the venous dilatation Balloon model of Buxton and Frank. We show that decreasing the cerebral blood flow (CBF) baseline value, or the CBF increase fraction, results in a decrease of the BOLD signal and an increase of the lactate peak during a sustained activation. Baseline lactate and PCr levels are not significantly affected by CBF baseline reduction, but are altered even by a moderate decrease of mitochondrial respiration. Decreasing the total Cr and PCr concentration reduces the BOLD signal after the initial overshoot. In conclusion, we suggest that the coupled use of BOLD fMRI and MRS could contribute to a better understanding of the neurovascular and metabolic decoupling in gliomas. (shrink)

The size and organization of the brain are determined by the activity of progenitor cells early in development. Key mechanisms regulating progenitor cell biology involve miRNAs. These small noncoding RNA molecules bind mRNAs with high specificity, controlling their abundance and expression. The role of miRNAs in brain development has been studied extensively, but their involvement at early stages remained unknown until recently. Here, recent findings showing the important role of miRNAs in the earliest phases of brain development (...) are reviewed, and it is discussed how loss of specific miRNAs leads to pathological conditions, particularly adult and pediatric brain tumors. Let‐7 miRNA downregulation and the initiation of embryonal tumors with multilayered rosettes (ETMR), a novel link recently discovered by the laboratory, are focused upon. Finally, it is discussed how miRNAs may be used for the diagnosis and therapeutic treatment of pediatric brain tumors, with the hope of improving the prognosis of these devastating diseases. (shrink)

Considerable progress has been made toward understanding the involvement of recoverin in a cancer-associated retinopathy (CAR) that results in blindness. We describe the expression of recoverin in tumors of individuals afflicted with CAR, characterize the immunological response towards recoverin in these patients, and demonstrate how the disease can be induced in rodents using recoverin as an immunogen.

The ability to image the human brain has provided a new perspective for neuropsychologists in their efforts to understand, diagnose, and treat insults to the human brain that might occur as the result of stroke, tumor, traumatic injury, degenerative disease, or errors in development. These new ®ndings are the major theme of this special issue. In our article, we consider brain networks that carry out the functions of attention. We outline several such networks that have been (...) studied in normal and pathological states. These include networks for orienting to sensory stimuli, for maintaining the alert state, and for orchestrating volitional control. (shrink)

Mutations in growth factor receptor signaling pathways are common in cancer cells, including the highly lethal brain tumor glioblastoma (GBM) where they drive tumor growth through mechanisms including altering the uptake and utilization of nutrients. However, the impact of changes in micro‐environmental nutrient levels on oncogenic signaling, tumor growth, and drug resistance is not well understood. We recently tested the hypothesis that external nutrients promote GBM growth and treatment resistance by maintaining the activity of mechanistic target (...) of rapamycin complex 2 (mTORC2), a critical intermediate of growth factor receptor signaling, suggesting that altered cellular metabolism is not only a consequence of oncogenic signaling, but also potentially an important determinant of its activity. Here, we describe the studies that corroborate the hypothesis and propose others that derive from them. Notably, this line of reasoning raises the possibility that systemic metabolism may contribute to responsiveness to targeted cancer therapies. (shrink)

Anthropology of Consciousness, EarlyView.

ABSTRACT I argue that this examination and appreciation for the shift to abductive reasoning should be extended to the intersection of neuroscience and novel brain-computer interfaces too. This paper highlights the implications of applying abductive reasoning to personalized implantable neurotechnologies. Then, it explores whether abductive reasoning is sufficient to justify insurance coverage for devices absent widespread clinical trials, which are better applied to one-size-fits-all treatments. INTRODUCTION In contrast to the classic model of randomized-control trials, often with a large number (...) of subjects enrolled, precision medicine attempts to optimize therapeutic outcomes by focusing on the individual.[i] A recent publication highlights the strengths and weakness of both traditional evidence-based medicine and precision medicine.[ii] Plus, it outlines a tension in the shift from evidence-based medicine’s inductive reasoning style (the collection of data to postulate general theories) to precision medicine’s abductive reasoning style (the generation of an idea from the limited data available).[iii] The paper’s main example is the application of precision medicine for the treatment of cancer.[iv] I argue that this examination and appreciation for the shift to abductive reasoning should be extended to the intersection of neuroscience and novel brain-computer interfaces too. As the name suggests, brain-computer interfaces are a significant advancement in neurotechnology that directly connects someone’s brain to external or implanted devices.[v] Among the various kinds of brain-computer interfaces, adaptive deep brain stimulation devices require numerous personalized adjustments to their settings during the implantation and computation stages in order to provide adequate relief to patients with treatment-resistant disorders. What makes these devices unique is how adaptive deep brain stimulation integrates a sensory component to initiate the stimulation. While not commonly at the level of sophistication as self-supervising or generative large language models,[vi] they currently allow for a semi-autonomous form of neuromodulation. This paper highlights the implications of applying abductive reasoning to personalized implantable neurotechnologies. Then, it explores whether abductive reasoning is sufficient to justify insurance coverage for devices absent widespread clinical trials, which are better applied to one-size-fits-all treatments.[vii] ANALYSIS I. The State of Precision Medicine in Oncology and the Epistemological Shift While a thorough overview of precision medicine for the treatment of cancer is beyond the scope of this article, its practice can be roughly summarized as identifying clinically significant characteristics a patient possesses (e.g., genetic traits) to land on a specialized treatment option that, theoretically, should benefit the patient the most.[viii] However, in such a practice of stratification patients fall into smaller and smaller populations and the quality of evidence that can be applied to anyone outside these decreases in turn.[ix] As inductive logic helps to articulate, the greater the number of patients that respond to a particular therapy the higher the probability of its efficacy. By straying from this logical framework, precision medicine opens the treatment of cancer to more uncertainty about the validity of these approaches to the resulting disease subcategories.[x] Thus, while contemporary medical practices explicitly describe some treatments as “personalized”, they ought not be viewed as inherently better founded than other therapies.[xi] A relevant contemporary case of precision medicine out of Norway focuses on the care of a patient with cancer between the ventricles of the heart and esophagus, which had failed to respond to the standard regimen of therapies over four years.[xii] In a last-ditch effort, the patient elected to pay out-of-pocket for an experimental immunotherapy (nivolumab) at a private hospital. He experienced marked improvements and a reduction in the size of the tumor. Understandably, the patient tried to pursue further rounds of nivolumab at a public hospital. However, the hospital initially declined to pay for it given the “lack of evidence from randomised clinical trials for this drug relating to this [patient’s] condition.”[xiii] In rebuttal to this claim, the patient countered that he was actually similar to a subpopulation of patients who responded in “open‐label, single arm, phase 2 studies on another immune therapy drug” (pembrolizumab).[xiv] Given this interpretation of the prior studies and the patient’s response, further rounds of nivolumab were approved. Had the patient not had improvements in the tumor’s size following a round of nivolumab, then pembrolizumab’s prior empirical evidence in isolation would have been insufficient, inductively speaking, to justify his continued use of nivolumab.[xv] The case demonstrates a shift in reasoning from the traditional induction to abduction. The phenomenon of ‘cancer improvement’ is considered causally linked to nivolumab and its underlying physiological mechanisms.[xvi] However, “the weakness of abductions is that there may always be some other better, unknown explanation for an effect. The patient may for example belong to a special subgroup that spontaneously improves, or the change may be a placebo effect. This does not mean, however, that abductive inferences cannot be strong or reasonable, in the sense that they can make a conclusion probable.”[xvii] To demonstrate the limitations of relying on the abductive standard in isolation, commentators have pointed out that side effects in precision medicine are hard to rule out as being related to the initial intervention itself unless trends from a group of patients are taken into consideration.[xviii] As artificial intelligence (AI) assists the development of precision medicine for oncology, this uncertainty ought to be taken into consideration. The implementation of AI has been crucial to the development of precision medicine by providing a way to combine large patient datasets or a single patient with a large number of unique variables with machine learning to recommend matches based on statistics and probability of success upon which practitioners can base medical recommendations.[xix] The AI is usually not establishing a causal relationship[xx] – it is predicting. So, as AI bleeds into medical devices, like brain-computer interfaces, the same cautions about using abductive reasoning alone should be carried over. II. Responsive Neurostimulation, AI, and Personalized Medicine Like precision medicine in cancer treatment, computer-brain interface technology similarly focuses on the individual patient through personalized settings. In order to properly expose the intersection of AI, precision medicine, abductive reasoning, and implantable neurotechnologies, the descriptions of adaptive deep brain stimulation systems need to deepen.[xxi] As a broad summary of adaptive deep brain stimulation, to provide a patient with the therapeutic stimulation, a neural signal, typically referred to as a local field potential,[xxii] must first be detected and then interpreted by the device. The main adaptive deep brain stimulation device with premarket approval, the NeuroPace Responsive Neurostimulation system, is used to treat epilepsy by detecting and storing “programmer-defined phenomena.”[xxiii] Providers can optimize the detection settings of the device to align with the patient’s unique electrographic seizures as well as personalize the reacting stimulation’s parameters.[xxiv] The provider adjusts the technology based on trial and error. One day machine learning algorithms will be able to regularly aid this process in myriad ways, such as by identifying the specific stimulation settings a patient may respond to ahead of time based on their electrophysiological signatures.[xxv] Either way, with AI or programmers, adaptive neurostimulation technologies are individualized and therefore operate in line with precision medicine rather than standard treatments based on large clinical trials. Contemporary neurostimulation devices are not usually sophisticated enough to be prominent in AI discussions where the topics of neural networks, deep learning, generative models, and self-attention dominate the conversation. However, implantable high-density electrocorticography arrays (a much more sensitive version than adaptive deep brain stimulation systems use) have been used in combination with neural networks to help patients with neurologic deficits from a prior stroke “speak” through a virtual avatar.[xxvi] In some experimental situations, algorithms are optimizing stimulation parameters with increasing levels of independence.[xxvii] An example of neurostimulation that is analogous to the use of nivolumab in Norway surrounds a patient in the United States who was experiencing both treatment-resistant OCD and temporal lobe epilepsy.[xxviii]Given the refractory nature of her epilepsy, implantation of an adaptive deep brain stimulation system was indicated. As a form of experimental therapy, her treatment-resistant OCD was also indicated for the off-label use of an adaptive deep brain stimulation set-up. Another deep brain stimulation lead, other than the one implanted for epilepsy, was placed in the patient’s right nucleus accumbens and ventral pallidum region given the correlation these nuclei had with OCD symptoms in prior research. Following this, the patient underwent “1) ambulatory, patient-initiated magnet-swipe storage of data during moments of obsessive thoughts; (2) lab-based, naturalistic provocation of OCD-related distress (naturalistic provocation task); and (3) lab-based, VR [virtual reality] provocation of OCD-related distress (VR provocation task).”[xxix] Such signals were used to identify when to deliver the therapeutic stimulation in order to counter the OCD symptoms. Thankfully, following the procedure and calibration the patient exhibited marked improvements in their OCD symptoms and recently shared her results publicly.[xxx] In both cases, there is a similar level of abductive justification for the efficacy of the delivered therapy. In the case study in which the patient was treated with adaptive deep brain stimulation, they at least had their neural activity tested in various settings to determine the optimum parameters for treatment to avoid them being based on guesswork. Additionally, the adaptive deep brain stimulation lead was already placed before the calibration trials were conducted, meaning that the patient had already taken on the bulk of the procedural risk before the efficacy could be determined. Such an efficacy test could have been replicated in the first patient’s cancer treatment, had it been biopsied and tested against the remaining immunotherapies in vitro. Yet, in the case of cancer with few options, one previous dose of a drug that appeared to work on the patient may justify further doses. However, as the Norwegian case presents, corroboration with known responses to a similar drug (from a clinical trial) could be helpful to validate the treatment strategy. (It should be noted that both patients were resigned to these last resort options regardless of the efficacy of treatment.) There are some elements of inductive logic seen with adaptive deep brain stimulation research in general. For example, abductively the focus could be that patient X’s stimulation parameters are different from patient Y’s and patient Z’s. In contrast, when grouped as subjects who obtained personalized stimulation, patients X, Y, and Z demonstrate an inductive aspect to this approach’s safety and/or efficacy. The OCD case holds plenty of abductive characteristics in line with precision medicine’s approach to treating cancer and as more individuals try the method, there will be additional data. With the gradual integration of AI into brain-computer interfaces in the name of efficacy, this reliance on abduction will continue, if not grow, over time. Moving forward, if a responsive deep brain stimulation treatment is novel and individualized (like the dose of nivolumab) and there is some other suggestion of efficacy (like clinical similarities to other patients in the literature), then it may justify insurance coverage for the investigative intervention, absent other unrelated reasons to deny it. III. Ethical Implications and Next Steps While AI’s use in oncology and neurology is not yet as prominent as its use in other fields (e.g., radiology), it appears to be on the horizon for both.[xxxi] AI can be found in both the functioning of the neurotechnologies as well as the implementation of precision medicine. The increasing use of AI may serve to further individualize both oncologic and neurological therapies. Given these implications and the handful of publications cited in this article, it is important to have a nuanced evaluation of how these treatments, which heavily rely on abductive justification, ought to be managed. The just use an abductive approach may be difficult as AI infused precision medicine is further pursued. At baseline, such technology relies on a level of advanced technology literacy among the general public and could exclude populations who lack access to basic technological infrastructure or know-how from participation.[xxxii] Even among nations with adequate infrastructure, as more patients seek out implantable neurotechnologies, which require robust healthcare resources, the market will favor patient populations that can afford this complex care.[xxxiii] If patients already have the means to pay for an initial dose/use of a precision medicine product out of pocket, should insurance providers be required to cover subsequent treatments?[xxxiv] That is, if a first dose of a cancer drug or a deep brain stimulator over its initial battery life is successful, patients may feel justified in having the costs of further treatments covered. The Norwegian patient’s experience implies there is a precedent for the idea that some public insurance companies ought to cover successful cancer therapies, however, insurance companies may not all see themselves as obligated to cover neurotechnologies that rely on personalized settings or that are based on precision/abductive research more than on clinical trials. CONCLUSION The fact that the cases outlined above rely on abductive style of reasoning implies that there may not be as strong a justification for coverage by insurance, as they are both experimental and individualized, when compared to the more traditional large clinical trials in which groups have the same or a standardized protocol (settings/doses). If a study is examining the efficacy of a treatment with a large cohort of patients or with different experimental groups/phases, insurance companies may conclude that the resulting symptom improvements are more likely to be coming from the devices themselves. A preference for inductive justification may take priority when ruling in favor of funding someone’s continued use of an implantable neurostimulator. There are further nuances to this discussion surrounding the classifications of these interventions as research versus clinical care that warrant future exploration, since such a distinction is more of a scale[xxxv] than binary and could have significant impacts on the “right-to-try” approach to experimental therapies in the United States.[xxxvi] Namely, given the inherent limitations of conducting large cohort trials for deep brain stimulation interventions on patients with neuropsychiatric disorders, surgically innovative frameworks that blend abductive and inductive methodologies, like with sham stimulation phases, have traditionally been used.[xxxvii] Similarly, for adaptive brain-computer interface systems, if there are no large clinical trials and instead only publications that demonstrate that something similar worked for someone else, then, in addition to the evidence that the first treatment/dose worked for the patient in question, the balance of reasoning would be valid and arguably justify insurance coverage. As precision approaches to neurotechnology become more common, frameworks for evaluating efficacy will be crucial both for insurance coverage and for clinical decision making. ACKNOWLEDGEMENT This article was originally written as an assignment for Dr. Francis Shen’s “Bioethics & AI” course at Harvard’s Center for Bioethics. I would like to thank Dr. Shen for his comments as well as my colleagues in the Lázaro-Muñoz Lab for their feedback. - [i] Jonathan Kimmelman and Ian Tannock, “The Paradox of Precision Medicine,” Nature Reviews. Clinical Oncology 15, no. 6 (June 2018): 341–42, https://doi.org/10.1038/s41571-018-0016-0. [ii] Henrik Vogt and Bjørn Hofmann, “How Precision Medicine Changes Medical Epistemology: A Formative Case from Norway,” Journal of Evaluation in Clinical Practice 28, no. 6 (December 2022): 1205–12, https://doi.org/10.1111/jep.13649. [iii] David Barrett and Ahtisham Younas, “Induction, Deduction and Abduction,” Evidence-Based Nursing 27, no. 1 (January 1, 2024): 6–7, https://doi.org/10.1136/ebnurs-2023-103873. [iv] Vogt and Hofmann, “How Precision Medicine Changes Medical Epistemology,” 1208. [v] Wireko Andrew Awuah et al., “Bridging Minds and Machines: The Recent Advances of Brain-Computer Interfaces in Neurological and Neurosurgical Applications,” World Neurosurgery, May 22, 2024, S1878-8750(24)00867-2, https://doi.org/10.1016/j.wneu.2024.05.104. [vi] Mark Riedl, “A Very Gentle Introduction to Large Language Models without the Hype,” Medium (blog), May 25, 2023, https://mark-riedl.medium.com/a-very-gentle-introduction-to-large-language-models-without-the-hype-5 f67941fa59e. [vii] David E. Burdette and Barbara E. Swartz, “Chapter 4 - Responsive Neurostimulation,” in Neurostimulation for Epilepsy, ed. Vikram R. Rao (Academic Press, 2023), 97–132, https://doi.org/10.1016/B978-0-323-91702-5.00002-5. [viii] Kimmelman and Tannock, 2018. [ix] Kimmelman and Tannock, 2018. [x] Simon Lohse, “Mapping Uncertainty in Precision Medicine: A Systematic Scoping Review,” Journal of Evaluation in Clinical Practice 29, no. 3 (April 2023): 554–64, https://doi.org/10.1111/jep.13789. [xi] Kimmelman and Tannock, “The Paradox of Precision Medicine.” [xii] Vogt and Hofmann, 1206. [xiii] Vogt and Hofmann, 1206. [xiv] Vogt and Hofmann, 1206. [xv] Vogt and Hofmann, 1207. [xvi] Vogt and Hofmann, 1207. [xvii] Vogt and Hofmann, 1207. [xviii] Vogt and Hofmann, 1210. [xix] Mehar Sahu et al., “Chapter Three - Artificial Intelligence and Machine Learning in Precision Medicine: A Paradigm Shift in Big Data Analysis,” in Progress in Molecular Biology and Translational Science, ed. David B. Teplow, vol. 190, 1 vols., Precision Medicine (Academic Press, 2022), 57–100, https://doi.org/10.1016/bs.pmbts.2022.03.002. [xx] Stefan Feuerriegel et al., “Causal Machine Learning for Predicting Treatment Outcomes,” Nature Medicine 30, no. 4 (April 2024): 958–68, https://doi.org/10.1038/s41591-024-02902-1. [xxi] Sunderland Baker et al., “Ethical Considerations in Closed Loop Deep Brain Stimulation,” Deep Brain Stimulation 3 (October 1, 2023): 8–15, https://doi.org/10.1016/j.jdbs.2023.11.001. [xxii] David Haslacher et al., “AI for Brain-Computer Interfaces,” 2024, 7, https://doi.org/10.1016/bs.dnb.2024.02.003. [xxiii] Burdette and Swartz, “Chapter 4 - Responsive Neurostimulation,” 103–4; “Premarket Approval (PMA),” https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P100026. [xxiv] Burdette and Swartz, “Chapter 4 - Responsive Neurostimulation,” 104. [xxv] Burdette and Swartz, 126. [xxvi] Sean L. Metzger et al., “A High-Performance Neuroprosthesis for Speech Decoding and Avatar Control,” Nature 620, no. 7976 (August 2023): 1037–46, https://doi.org/10.1038/s41586-023-06443-4. [xxvii] Hao Fang and Yuxiao Yang, “Predictive Neuromodulation of Cingulo-Frontal Neural Dynamics in Major Depressive Disorder Using a Brain-Computer Interface System: A Simulation Study,” Frontiers in Computational Neuroscience 17 (March 6, 2023), https://doi.org/10.3389/fncom.2023.1119685; Mahsa Malekmohammadi et al., “Kinematic Adaptive Deep Brain Stimulation for Resting Tremor in Parkinson’s Disease,” Movement Disorders 31, no. 3 (2016): 426–28, https://doi.org/10.1002/mds.26482. [xxviii] Young-Hoon Nho et al., “Responsive Deep Brain Stimulation Guided by Ventral Striatal Electrophysiology of Obsession Durably Ameliorates Compulsion,” Neuron 0, no. 0 (October 20, 2023), https://doi.org/10.1016/j.neuron.2023.09.034. [xxix] Nho et al. [xxx] Nho et al.; Erik Robinson, “Brain Implant at OHSU Successfully Controls Both Seizures and OCD,” OHSU News, accessed March 3, 2024, https://news.ohsu.edu/2023/10/25/brain-implant-at-ohsu-successfully-controls-both-seizures-and-ocd. [xxxi] Awuah et al., “Bridging Minds and Machines”; Haslacher et al., “AI for Brain-Computer Interfaces.” [xxxii] Awuah et al., “Bridging Minds and Machines.” [xxxiii] Sara Green, Barbara Prainsack, and Maya Sabatello, “The Roots of (in)Equity in Precision Medicine: Gaps in the Discourse,” Personalized Medicine 21, no. 1 (January 2024): 5–9, https://doi.org/10.2217/pme-2023-0097. [xxxiv] Green, Prainsack, and Sabatello, 7. [xxxv] Robyn Bluhm and Kirstin Borgerson, “An Epistemic Argument for Research-Practice Integration in Medicine,” The Journal of Medicine and Philosophy: A Forum for Bioethics and Philosophy of Medicine 43, no. 4 (July 9, 2018): 469–84, https://doi.org/10.1093/jmp/jhy009. [xxxvi] Vijay Mahant, “‘Right-to-Try’ Experimental Drugs: An Overview,” Journal of Translational Medicine 18 (June 23, 2020): 253, https://doi.org/10.1186/s12967-020-02427-4. [xxxvii] Michael S. Okun et al., “Deep Brain Stimulation in the Internal Capsule and Nucleus Accumbens Region: Responses Observed during Active and Sham Programming,” Journal of Neurology, Neurosurgery & Psychiatry 78, no. 3 (March 1, 2007): 310–14, https://doi.org/10.1136/jnnp.2006.095315. (shrink)

RESUMO O Discourse Diversity Database (3D) é um corpus desenvolvido para a pesquisa em linguística clínica. Ele consiste de amostras de fala oral de três gêneros diferentes: narrativas induzidas por imagens, histórias pessoais e instruções baseadas em imagens. As subdivisões do 3D incluem gravações de falantes de russo de três grupos independentes: pessoas com tumores cerebrais antes e depois da remoção do tumor, pessoas com esquizofrenia e indivíduos neurologicamente saudáveis. O presente artigo é dedicado à descrição do procedimento de (...) coleta de dados, do esquema de anotação e das características específicas de cada subdivisão do corpus. (shrink)

Brain tumors are a common form of solid tumors in children and, unfortunately, they are characterized by a very uncertain prognosis. The treatment of this pathology often includes one or more very invasive surgical procedures, quite often in the very first steps of the treatment. Cases of brain tumors in children represent one of the greatest challenges for health care professionals in the domain of pediatric neurosurgery. This is clearly due to the complexity of the therapeutic plan, but (...) also to the nature of the bond that is established between the child, the parents, and the members of the staff during the often-dramatic initial phase of the illness. In this phenomenological-hermeneutic study, we explore both the emotional and organizational needs, as well as the available professional and personal resources of the staff in the Neurosurgery ward of the Meyer Children’s Hospital in Florence. The ward staff, composed of 7 surgeons, a pediatric neuro-oncologist, 12 nurses, and 4 auxiliary health care professionals, underwent in-depth interviews that were recorded. The recordings were then transcribed and submitted to content analysis according to COREQ standards. A complex picture of emotional as well as organizational demands emerged from the data. Shared experiences were pointed out, together with more specific and idiosyncratic contents characteristic of different professional roles. The focus of the present paper was twofold, first, we considered the needs that are overtly expressed by the staff, and then we discussed the main sources of their motivational drives. We found that the latter is mainly found in the quality of the therapeutic bond that is established with the children and the family members, together with the deep interest in one’s own professional activity and the effective complementarity and integration of the personal and professional qualities of the staff members within the multidisciplinary caring group. (shrink)

While primary malignant brain tumors account for only two percent of all adult cancers, these neoplasms cause a disproportionate amount of cancer-related disabilities and death. The five-year survival rates for brain tumors are the third lowest among all types of cancer. Malignant gliomas comprise the most common types of primary central nervous system tumors and have a combined incidence of five to eight cases per 100,000 people. The median survival rate of conservatively treated patients with malignant gliomas is (...) 14 weeks; with surgical resection alone, 20 weeks; with surgery and radiation, 36 weeks; and with the addition of newer biochemotherapies such as temozolomide and bevacizumab, upward of 14-18 months.The profound cost of caring for terminally ill patients with primary malignant brain tumors raises ethical considerations for the American public; the stewardship of health care dollars for the population at large maintains a juxtaposed tension against a dynamic, necessary balance of hope, care, rehabilitation and research efforts for affected patients and their advocates. (shrink)

For focal neurodegenerative diseases or brain tumors, localized delivery of protein or genetic vectors may be sufficient to alleviate symptoms, halt disease progression, or even cure the disease. One may circumvent the limitation imposed by the blood-brain barrier by transplantation of genetically altered cell grafts or focal inoculation of virus or protein. However, permanent gene replacement therapy for diseases affecting the entire brain will require global delivery of genetic vectors. The neurotoxicity of currently available viral vectors and (...) the transient nature of transgene expression invivomust be overcome before their use in human gene therapy becomes clinically applicable. (shrink)

It’s common in this world, for diagnoses to be confused. This grey, oblique world is the “World of Brain Tumors” from which these narratives are written, a world I entered when a tangerine–sized tumor was found on my temporal lobe. Each narrative illustrates this world in which everything is covered in a thick film rendering things once obvious, now unknown. Parents are asked to choose treatment plans for their children, plans that will inevitably alter their child’s quality of (...) life but in ways they cannot determine or even imagine. Parents are asked to play God. Most of the parents who share their stories in this collection, parents of PBT (pediatric brain tumor) patients have to walk the line of trying to not disrupt their relationships with their physicians, wanting the best for their child, and facing the decision to follow their gut or go with advised treatment plans. (shrink)

When the language-dominant hemisphere is damaged by a focal lesion, the brain may reorganize the language network through functional and structural changes known as adaptive plasticity. Adaptive plasticity is documented for triggers including ischemic, tumoral, and epileptic focal lesions, with effects in clinical practice. Many questions remain regarding language plasticity. Different lesions may induce different patterns of reorganization depending on pathologic features, location in the brain, and timing of onset. Neuroimaging provides insights into language plasticity due to its (...) non-invasiveness, ability to image the whole brain, and large-scale implementation. This review provides an overview of language plasticity on MRI with insights for patient care. First, we describe the structural and functional language network as depicted by neuroimaging. Second, we explore language reorganization triggered by stroke, brain tumors, and epileptic lesions and analyze applications in clinical diagnosis and treatment planning. By comparing different focal lesions, we investigate determinants of language plasticity including lesion location and timing of onset, longitudinal evolution of reorganization, and the relationship between structural and functional changes. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:An Encounter with the Art and Science of MedicineAnonymous Five“Let Nothing Upset YouLet Nothing Frighten YouEverything is ChangingOnly God is Changeless”—St. Theresa of AvilaSt. Teresa’s prayer is on the front cover of each of four binders dedicated to storing insurance authorizations, studies, references, and reports about our daughter’s brain tumor treatment. They represent our experience, what we learned, the information we were given, and the information we (...) sought out. I kept them in case our daughter ever wanted to understand how my husband and I arrived at a decision for her treatment that was in direct opposition to the strong recommendation of her primary treatment team of physicians.On December 10, 2003, I received an urgent call from our daughter’s neurologist requesting that we meet with the doctor late that afternoon. For six months prior to that appointment, our daughter had been telling us about odd sensations with breathing, nausea, and balance. Sometimes she would seem extremely distressed for a short period of time or report that her friends told her about doing or saying things that didn’t make sense and that she didn’t remember. We consulted a series of physicians as her symptoms became steadily more intense and more prevalent. Our family practice physician referred us to an allergy specialist and a pulmonologist. There were a number of tests for allergies and lung problems. As the tests and treatments did not help, our daughter became increasingly unwilling to go to doctor’s appointments. My husband and I were confused and deeply concerned about the lack of progress. The next series of referrals included a gastroenterologist and a neurologist. The gastroenterologist suggested our daughter had partial–complex epilepsy, concurred with our plan to see a neurologist, and mentioned she should have an MRI.I remember the neurologist putting the MRI scans up, pointing to the large dark spot which he called a “large mass” (5 cm), that could be either a cluster of blood vessels or a neoplasm. He said his office had arranged for us to meet a neurosurgeon the following day. We all remember the same thing about that visit—the image of the large dark mass on the scan—and the neurologists flat, brisk tone. We met with the neuro-surgeon the next day. Her team was kind and sympathetic—she was positive, up beat and direct. She did not think this mass was blood vessels. She thought it was a large tumor that needed to be removed right away. Our daughters surgery was scheduled for the following Friday—December 19, 2003. She had turned 15 on November 5.Four and a half hours after our daughter was wheeled into the operating room, her surgeon told us they had removed 98% of the tumor. She said there was no cure, but there was a good prognosis based on the surgical outcome. Several days later, she called us and said she had more data, and it looked like the resection was closer to 90%. The first pathology report, a “first impression” directly after surgery, described our daughter’s tumor as an astrocytoma, probably high grade. Three weeks after surgery, we met with a panel of doctors—two oncologists and radiologist—who explained that based on the final pathology report, our daughter’s tumor was classified as an ependymoma, grade 2. We were dismayed. First, there had been the change in the estimated success of the resection and now a complete shift in both grade and tumor type.The team recommended radiation to follow her surgery, which they said was standard treatment. We began to try to inform ourselves about her tumor. Her father, an agronomist, did an extensive search in PubMed to evaluate and sort through the literature on low–grade gliomas and radiation. What he could find was inconclusive and grim. Most reports in the literature suggested at best delayed mortality at five years after radiation. [End Page E7] Meanwhile, our daughter went through a spinal MRI and the preparatory “fitting” of the mask to immobilize her head during radiation.E7I consulted with a friend who had worked as an EKG tech. She urged... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:'Difficult Patient':A Reflective EssayDaniel McFarlandThe patient who sat across from me knew too much about all brain tumors. According to her, she would never know enough about the one sitting uncomfortably close to her brain's temporal lobe. In her quest for the 'right' answer to her meningioma problem, she became certain that its surgical removal would upend her life, leaving her in neurological taters.She was a small (...) business owner of a practice dedicated to medical massage. Indubitably, she had helped countless clients heal themselves of medical mishaps and avoid or recover from the tyranny of [End Page E13] a medical community that did not always provide respectable, hospitable care. She was certain a craniotomy would end her business, nullifying everything she had spent her life building. She became fluent in the legalese needed to transfer or sell her business in anticipation of surgery. To stave off losing her life's work from a surgical mishap, she sought opinions from a dozen neurosurgeons. They reassured her that a routine surgery like this would be effective with little chance of neurological collateral damage. She did not believe them. In her business she had treated numerous exhausted professionals. Many surgeons with whom she worked professionally frequently referred patients to her. She had seen the poor self-care that many surgeons and doctors brought on themselves in the form of unrelenting stress, drinking, bad eating habits, and even drugs. This made her nervous and untrusting about the care she could receive at the hands of an overworked or impaired surgeon. She scheduled appointments with every neurosurgeon she could find and interviewed them relentlessly, looking for the slightest sign of incompetence, unprofessionalism, antipathy, or lapse in compassion. Given her insistence and dogged nature, she usually found what she was looking for. She would bring her research to the appointments and interview the neurosurgeons on what other doctors had opined. If they were incredulous of research she brought or a technique on which she inquired, they were summarily dismissed.At first glance, which is likely all that she got from many of her visits, these encounters put a spotlight on a 'difficult' patient refusing care. The deeper look that my patient deserved revealed a personal narrative of the oldest child who survived a broken home riddled with drug use and prostitution. She learned to rely on only herself for protection. She took unapologetic control of her fate. Her own mother had at one time offered my patient work as a prostitute. Her father was no better in providing protection and a decent upbringing. He had left her as an eight-year-old with the neglectful mother and four younger siblings to fend for herself, which she did against the odds. She suffered physical, emotional, and spiritual abuse.As an adult, her strong sense of selfhood and boundaries allowed her to have a guarded relationship with both of her parents at a comfortable emotional distance. Her mission and passionate drive to help others heal saved her life. In healing others, she was healing herself. Importantly, her experience marked for her indelibly that while she could do this for herself, others were not reliable and could not heal her. She had only ever trusted and relied upon herself. She was the only one who had never let her down. She was terrified that this might be the first time. The potential surgery risked her cognition, physical capacities, and ability to care for herself. The risk was too great.We met numerous times, uncovering her past, reliving the stories of her tumultuous background, and examining how she established her place in the world away from the horrors of her insecure childhood. She took in my reaction to her stories and saw the horror on my face when I tried to imagine a world where one's parents were not only neglectful but the source of danger. Through my reaction, she may have begun to have some compassion for her own story and put the pieces together. One several occasions, she became enraged when I didn't meet her expectations, or I didn't entertain the diatribe of neurosurgical scholarly work.On one of those... (shrink)

This article comments on the following previously published article: Moncrieff, J., “ It Was the Brain Tumor That Done It!” Szasz and Wittgenstein on the Importance of Distinguishing Disease from Behavior and Implications for the Nature of Mental Disorder. Philosophy, Psychiatry, & Psychology, 27, 169–181.Joanna Moncrieff’s philosophical views on the nature of mental illness represent in many ways the enduring legacy of Thomas Szasz in philosophy of psychiatry. She articulates a defense of Szaszian thinking about disease, with connections (...) to Wittgenstein’s philosophy, that is probably as compelling a defense as a contemporary student of philosophy is likely to find. However, Moncrieff’s... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Life in LimboM. ChiuWhen my son was 7 years old, he began complaining of headaches. They were frequent, but never seemed severe. “I have a headache!” was always followed by “Can I watch TV?” I didn’t believe the pain was real until it woke him up in the middle of the night. I knew then that something must be wrong. I approached our pediatrician, who said it sounded like (...) migraines, but we should order an MRI to rule anything out. The appointment was scheduled several months in advance, and I always had the urge to cancel it. I was pretty sure my son just wanted to watch TV. The pediatrician told me I might as well do the MRI. He told me that if we skipped it and something was wrong, I would never be able to live with the regret. We kept the Monday morning appointment, and went to the MRI expecting reassurance that nothing was wrong. Instead, we got a phone call later that day. They needed to see us on immediately, but wouldn’t tell me why. Of course, I knew something was wrong. “Is it a tumor?” I asked. “This isn’t something we can discuss on the phone” was the answer I got. An appointment was scheduled for Wednesday. Two days might be “immediately” to medical professionals, but to a parent who just heard that her child had an abnormal MRI, it was an eternity. I planned my son’s funeral in those two days.Our meeting with the Neurologist began with reviewing the MRI. “See this spot here? It shouldn’t be there”. A tumor. 1 ½ × 1 ½ × 2 ½ cm tumor, in the right thalamus. Small, they said. Looks like a Low Grade Glioma they said. The kind of tumor you want to have, if you have to have a brain tumor. A biopsy was scheduled for two weeks later. The [End Page E2] biopsy confirmed it was a Juvenile Pilocytic Astrocytoma (JPA). The neurosurgeon was confident she could remove all of the tumor. We were at one of the best Children’s Hospitals in the world. We were in good hands.A few days before the surgery, a friend who is a medical doctor suggested we get a second opinion. “It couldn’t hurt, it could help”, my husband said. Fortunately, he just sold a start–up company, and was planning to take a few months off from work before starting his next venture. He had time to research, talk to friends in the medical field and make phone calls.Our second opinion from another leading hospital reviewed the MRI’s with us. The neurosurgeon asked, “Did they say tumor? One?” Yes, they did. “See this here?” he said, pointing to a second spot on the MRI. He said it was possibly a second tumor, or more likely, an extension of the first. It was in inoperable location. Surgery wasn’t an option. Chemo would be our best choice. Why would we cut into our son’s brain to remove part of the tumor when he would need to do chemo anyway? Why not try chemo first?I would like to say that we do not fault our original neuro–oncology team for missing this second abnormality. It is hard to notice an ant in the room when there is an elephant staring at you. People make mistakes, and tumors don’t always look the same. That’s what second opinions are for. That is why doctors should encourage patients to get second opinions.We scheduled the surgery for port implantation, and got busy educating ourselves about chemo regimes. It was going to be a long journey. 18 months of transfusions with a pretty low success rate and a high rate of secondary complications. Unsure if we were doing the right thing, we got a third opinion. I am so grateful that my husband was between jobs and had time to devote to finding the best possible treatment for our son. We were financially stable and had great insurance. What do people do when they don’t have this luxury?By now, several months had passed since our first MRI. Our... (shrink)