Digital Phenotyping in Clinical Neurology

Internet-connected devices, including personal computers, smartphones, smartwatches, and voice assistants, have evolved into powerful multisensor technologies that billions of people interact with daily to connect with friends and colleagues, access and share information, purchase goods, play games, and navigate their environment. Digital phenotyping taps into the data streams captured by these devices to characterize and understand health and disease. The purpose of this article is to summarize opportunities for digital phenotyping in neurology, review studies using everyday technologies to obtain motor and cognitive information, and provide a perspective on how neurologists can embrace and accelerate progress in this emerging field.

From the Heart to the Brain: Building Bridges to a Better Future

This Presidential Address was delivered at the International Stroke Conference in March 2021, during the coronavirus pandemic. Dr Elkind, the President of the American Heart Association (AHA) at the time, is a vascular neurologist with a research focus on stroke epidemiology. This address interweaves personal reflections on a career in clinical neurology, stroke research, and public health with a discussion of the role of the AHA in improving cardiovascular health at multiple levels. Throughout its history, the AHA has had leaders representing many different areas of cardiovascular science and medicine, including stroke. More recently, its focus has expanded from a traditional emphasis on cardiovascular events illness and events, like heart disease and stroke, to an appreciation of the role of the vascular system in brain health, healthy aging, cognitive decline, and dementia. During the pandemic, as the bidirectional effects of the coronavirus on cardiovascular disease has been elucidated, the benefits of a broad and multidisciplinary approach to cardiovascular disease and public health have become more apparent than ever. In addition, with growing awareness of the disproportionate effects of the pandemic on communities of color in the United States and globally, the AHA has redoubled its focus on addressing the social determinants of health, including structural racism. Central to these efforts is the construction of bridges between the generation of scientific knowledge and action for the public good. Our success will depend on the combination of basic, translational, clinical and population research with programs of public and professional education, advocacy, and social action.

A Century of Brain Regeneration Phenomena and Neuromorphological Research Advances, 1890s–1990s—Examining the Practical Implications of Theory Dynamics in Modern Biomedicine

The modern thesis regarding the “structural plastic” properties of the brain, as reactions to injuries, to tissue damage, and to degenerative cell apoptosis, can hardly be seen as expendable in clinical neurology and its allied disciplines (including internal medicine, psychiatry, neurosurgery, radiology, etc.). It extends for instance to wider research areas of clinical physiology and neuropsychology which almost one hundred years ago had been described as a critically important area for the brain sciences and psychology alike. Yet the mounting evidence concerning the range of structural neuroplastic phenomena beyond the significant early 3 years of childhood has shown that there is a progressive building up and refining of neural circuits in adaptation to the surrounding environment. This review essay explores the history behind multiple biological phenomena that were studied and became theoretically connected with the thesis of brain regeneration from Santiago Ramón y Cajal’s pioneering work since the 1890s to the beginning of the American “Decade of the Brain” in the 1990s. It particularly analyzes the neuroanatomical perspectives on the adaptive capacities of the Central Nervous System (CNS) as well as model-like phenomena in the Peripheral Nervous System (PNS), which were seen as displaying major central regenerative processes. Structural plastic phenomena have assumed large implications for the burgeoning field of regenerative or restorative medicine, while they also pose significant epistemological challenges for related experimental and theoretical research endeavors. Hereafter, early historical research precursors are examined, which investigated brain regeneration phenomena in non-vertebrates at the beginning of the 20th century, such as in light microscopic studies and later in electron microscopic findings that substantiated the presence of structural neuroplastic phenomena in higher cortical substrates. Furthermore, Experimental physiological research in hippocampal in vivo models of regeneration further confirmed and corroborated clinical physiological views, according to which “structural plasticity” could be interpreted as a positive regenerative CNS response to brain damage and degeneration. Yet the underlying neuroanatomical mechanisms remained to be established and the respective pathway effects were only conveyed through the discovery of neural stem cells in in adult mammalian brains in the early 1990s. Experimental results have since emphasized the genuine existence of adult neurogenesis phenomena in the CNS. The focus in this essay will be laid here on questions of the structure and function of scientific concepts, the development of research schools among biomedical investigators, as well as the impact of new data and phenomena through innovative methodologies and laboratory instruments in the neuroscientific endeavors of the 20th century.

Understanding How to Strengthen the Neurology Pipeline With Insight From Undergraduate Neuroscience Students

Despite increased neuroscience interest at the undergraduate level, a significant shortage of neurologists in the United States (US) exists. To better understand how to generate more interest in neurology specifically at the undergraduate level, we conducted an anonymous cross-sectional online survey of 1085 undergraduates either in neuroscience courses or majoring/minoring in neuroscience from across the US to better understand their clinical neurology experiences and perspectives. The survey quantitatively and qualitatively assessed students’ clinical neurology exposure inside and outside of the classroom, research experiences and career goals. Students were from a broad spectrum of undergraduate institutions (public research university (40.8%), liberal arts College (29.7%) and private research university (29.0%). Most students (89.9%) were looking to pursue graduate studies; 56.9% reported wanting to be a physician and 17.8% expressed interest in obtaining an MD/PhD. Importantly, students reported first exposure to neuroscience at age 16 but felt that they could be exposed to neuroscience as early as 13. Half (50.5%) decided to major in neuroscience before college and a quarter (25.6%) decided to major in their first year of college. Despite high interest in clinical neurology exposure, less than one-third of students had spoken with or shadowed a neurologist, and only 13.6% had interacted with clinical neurology populations. Only 20.8% of students felt volunteer and internship opportunities were sufficiently available. Qualitative results include student perspectives from those who did and did not work with a neurologist, describing how they were or were not able to obtain such opportunities. We discuss translating the survey findings into actionable results with opportunities to target the undergraduate neuroscience interest to improve the neurology pipeline. We describe existing programs that could be integrated into everyday neurology practices and new approaches to learning and training to help leverage the significant undergraduate neuroscience interest. We also raise questions for further research, including exploring (1) how students learn of neurologic conditions/expand their knowledge about additional neurologic conditions, (2) whether qualitative investigation of the experiences of neuroscience undergraduates at specific institutions might provide additional insight, and (3) systems to maintain interest in neuroscience/neurology as students enter medical school.

Research challenges and opportunities in the Caribbean area: first bibliometric study in the French West Indies, from 1989 to 2018

Objective. To analyze, describe, and quantify the collaborations and scientific output of the two university teaching hospitals of Martinique and Guadeloupe, at the regional, national, and international level. Methods. A bibliometrics analysis was performed from the international databases Web of Science and PubMed, for the period from 1989 to 2018, inclusive (30 years). Three types of bibliometric indicators were used, namely quantitative indicators, performance indicators, and organization-specific indicators. Affiliations of the first and last authors were identified from PubMed. Results. Between 1989 and 2018, a total of 1 522 indexed articles were published with at least one author affiliated to either the University Hospital of Martinique (n = 827) or the University Hospital of Guadeloupe (n = 685). The majority of articles were in category Q1 (35.8% for Martinique and 35.2% for Guadeloupe). In Martinique, over the last 30 years, the three main research areas have been clinical neurology, ophthalmology, and surgery, together representing 28.7% of all research areas, with the highest number of articles published in the field of clinical neurology (n = 81). In the University Hospital of Guadeloupe, the area of hematology was largely represented, with 79 articles published. For both hospitals, the first and last authors of the article published were mainly from mainland France Conclusions. This quantitative analysis shows the development of medical and scientific research in Martinique and Guadeloupe over the last three decades, as well as the extent of their collaborative partnerships at the national and international levels.

Fyodor Mikhailovich Dostoyevsky between Moritz Heinrich Romberg and Armand Trousseau.

Fyodor M. Dostoyevsky (1821-1881) was a famous Russian writer born 200 years ago, important for the psychological depth and dramatic structure of his novels. Epilepsy was important in his life and creative process. Moritz H. Romberg (1795-1873) and Armand Trousseau (1801-1867) were two well-known physicians at the time who dedicated themselves to neurology. Its notoriety extended beyond the medical-scientific area, as exemplified by Dostoievski's letter. Although the occurrence of the meeting was controversial,3,4 its intention denotes their prestige. Romberg, known as the father of clinical neurology. Fyodor M. Dostoyevsky (1821-1881) foi um famoso escritor russo nascido há 200 anos, importante pela profundidade psicológica e estrutura dramática dos seus romances. A epilepsia foi importante na sua vida e no seu processo criativo. Moritz H. Romberg (1795-1873) e Armand Trousseau (1801-1867) eram dois médicos conhecidos na altura que se dedicavam à neurologia. A sua notoriedade estendeu-se para além da área médico-científica, como exemplificado pela carta de Dostoievski. Embora a ocorrência do encontro tenha sido controversa,3,4 a sua intenção denota o seu prestígio. Romberg, conhecido como o pai da neurologia clínica

Biological Mechanism-based Neurology and Psychiatry: a BACE1/2 and Downstream Pathway Model

: In Oncology, comprehensive Omics and functional enrichment studies led to an extensive profiling of (epi)genetic and neurobiological alterations that can be mapped onto a single tumor’s clinical phenotype and divergent clinical phenotypes expressing common pathophysiological pathways. Consequently, molecular pathway-based therapeutic interventions for different cancer typologies, namely tumor type- and site-agnostic treatments, have been developed, encouraging real-world implementation of a paradigm shift in medicine. Given the breakthrough nature of the new-generation translational research and drug development in Oncology, there is an increasing rationale to transfertilize this blueprint to other medical fields including Psychiatry and Neurology. To illustrate the emerging paradigm shift in neuroscience, we provide a state-of-the-art review of translational studies on the β-site amyloid precursor protein cleaving enzyme (BACE) and its most studied downstream effector, neuregulin, which are molecular orchestrators of distinct biological pathways involved in several neurological and psychiatric diseases. This body of data aligns with the evidence of a shared genetic/biological architecture among Alzheimer’s disease, schizoaffective and autism spectrum disorders. We engage in a speculative intellectual exercise gravitating around the BACE-related science, here used as paradigmatic case, to facilitating a forward-looking discussion about a potential first step towards the adoption of biological pathway-based, clinical symptom agnostic, categorization models in clinical Neurology and Psychiatry for precision medicine solutions. We draw a perspective whereby pathway-based therapeutic strategies could be catalyzed by high-throughput techniques, embedded in systems-scaled biology, neuroscience, and pharmacology approaches that will help overcome the constraints of traditional descriptive clinical symptom and syndrome-focused constructs in Neurology and Psychiatry.