Structural connectivity‐based topography of the human globus pallidus: Implications for therapeutic targeting in movement disorders

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Red nucleus structure and function: from anatomy to clinical neurosciences

The red nucleus (RN) is a large subcortical structure located in the ventral midbrain. Although it originated as a primitive relay between the cerebellum and the spinal cord, during its phylogenesis the RN shows a progressive segregation between a magnocellular part, involved in the rubrospinal system, and a parvocellular part, involved in the olivocerebellar system. Despite exhibiting distinct evolutionary trajectories, these two regions are strictly tied together and play a prominent role in motor and non-motor behavior in different animal species. However, little is known about their function in the human brain. This lack of knowledge may have been conditioned both by the notable differences between human and non-human RN and by inherent difficulties in studying this structure directly in the human brain, leading to a general decrease of interest in the last decades. In the present review, we identify the crucial issues in the current knowledge and summarize the results of several decades of research about the RN, ranging from animal models to human diseases. Connecting the dots between morphology, experimental physiology and neuroimaging, we try to draw a comprehensive overview on RN functional anatomy and bridge the gap between basic and translational research

In vivo probabilistic atlas of white matter tracts of the human subthalamic area combining track density imaging and optimized diffusion tractography

The human subthalamic area is a region of high anatomical complexity, tightly packed with tiny fiber bundles. Some of them, including the pallidothalamic, cerebello-thalamic, and mammillothalamic tracts, are relevant targets in functional neurosurgery for various brain diseases. Diffusion-weighted imaging-based tractography has been suggested as a useful tool to map white matter pathways in the human brain in vivo and non-invasively, though the reconstruction of these specific fiber bundles is challenging due to their small dimensions and complex anatomy. To the best of our knowledge, a population-based, in vivo probabilistic atlas of subthalamic white matter tracts is still missing. In the present work, we devised an optimized tractography protocol for reproducible reconstruction of the tracts of subthalamic area in a large data sample from the Human Connectome Project repository. First, we leveraged the super-resolution properties and high anatomical detail provided by short tracks track-density imaging (stTDI) to identify the white matter bundles of the subthalamic area on a group-level template. Tracts identification on the stTDI template was also aided by visualization of histological sections of human specimens. Then, we employed this anatomical information to drive tractography at the subject-level, optimizing tracking parameters to maximize between-subject and within-subject similarities as well as anatomical accuracy. Finally, we gathered subject level tracts reconstructed with optimized tractography into a large-scale, normative population atlas. We suggest that this atlas could be useful in both clinical anatomy and functional neurosurgery settings, to improve our understanding of the complex morphology of this important brain region

Interventional Radiological Management and Prevention of Complications after Pancreatic Surgery: Drainage, Embolization and Islet Auto-Transplantation

Pancreatic surgery still remains burdened by high levels of morbidity and mortality with a relevant incidence of complications, even in high volume centers. This review highlights the interventional radiological management of complications after pancreatic surgery. The current literature regarding the percutaneous drainage of fluid collections due to pancreatic fistulas, percutaneous transhepatic biliary drainage due to biliary leaks and transcatheter embolization (or stent–graft) due to arterial bleeding is analyzed. Moreover, also, percutaneous intra-portal islet auto-transplantation for the prevention of pancreatogenic diabetes in case of extended pancreatic resection is also examined. Moreover, a topic not usually treated in other similar reviewsas percutaneous intra-portal islet autotransplantation for the prevention of pancreatogenic diabetes in case of extended pancreatic resection is also one of our areas of focus. In islet auto-transplantation, the patient is simultaneously donor and recipient. Differently from islet allo-transplantation, it does not require immunosuppression, has no risk of rejection and is usually efficient with a small number of transplanted islets

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

Structural Connectivity-Based Parcellation of the Dopaminergic Midbrain in Healthy Subjects and Schizophrenic Patients

Background and objectives: Functional deregulation of dopaminergic midbrain regions is a core feature of schizophrenia pathophysiology. Anatomical research on primates suggests that these regions may be subdivided into distinct, topographically organized functional territories according to their connectivity to the striatum. The aim of the present work was the reconstruction of dopaminergic midbrain subregions in healthy subjects and schizophrenic patients and the evaluation of their structural connectivity profiles. Materials and Methods: A hypothesis-driven connectivity-based parcellation derived from diffusion tractography was applied on 24 healthy subjects and 30 schizophrenic patients to identify distinct territories within the human dopaminergic midbrain in vivo and non-invasively. Results: We identified a tripartite subdivision of dopaminergic midbrain, including limbic, prefrontal and sensorimotor territories. No significant differences in structural features or connectivity were found between subjects and patients. Conclusions: The parcellation scheme proposed herein may help to achieve detailed characterization of structural and functional anomalies of the dopaminergic midbrain in schizophrenic patients

Striatal topographical organization: Bridging the gap between molecules, connectivity and behavior

The striatum represents the major hub of the basal ganglia, receiving projections from the entire cerebral cortex and it is assumed to play a key role in a wide array of complex behavioral tasks. Despite being extensively investigated during the last decades, the topographical organization of the striatum is not well understood yet. Ongoing efforts in neuroscience are focused on analyzing striatal anatomy at different spatial scales, to understand how structure relates to function and how derangements of this organization are involved in various neuropsychiatric diseases. While being subdivided at the macroscale level into dorsal and ventral divisions, at a mesoscale level the striatum represents an anatomical continuum sharing the same cellular makeup. At the same time, it is now increasingly ascertained that different striatal compartments show subtle histochemical differences, and their neurons exhibit peculiar patterns of gene expression, supporting functional diversity across the whole basal ganglia circuitry. Such diversity is further supported by afferent connections which are heterogenous both anatomically, as they originate from distributed cortical areas and subcortical structures, and biochemically, as they involve a variety of neurotransmitters. Specifically, the cortico-striatal projection system is topographically organized delineating a functional organization which is maintained throughout the basal ganglia, subserving motor, cognitive and affective behavioral functions. While such functional heterogeneity has been firstly conceptualized as a tripartite organization, with sharply defined limbic, associative and sensorimotor territories within the striatum, it has been proposed that such territories are more likely to fade into one another, delineating a gradient-like organization along medio-lateral and ventro-dorsal axes. However, the molecular and cellular underpinnings of such organization are less understood, and their relations to behavior remains an open question, especially in humans. In this review we aimed at summarizing the available knowledge on striatal organization, especially focusing on how it links structure to function and its alterations in neuropsychiatric diseases. We examined studies conducted on different species, covering a wide array of different methodologies: from tract-tracing and immunohistochemistry to neuroimaging and transcriptomic experiments, aimed at bridging the gap between macroscopic and molecular levels

Cognitive and Mood Effect of Alpha-Lipoic Acid Supplementation in a Nonclinical Elder Sample: An Open-Label Pilot Study

Background: Memory disorders are common among elder people, and nonclinical cognitive decline is commonly experienced with age. Preclinical investigations have explored the possible role of alpha-lipoic acid (ALA), a known antioxidant compound abundant in vegetables and animal tissues, in reducing oxidative stress in the aging brain and preventing cognitive decline. However, clinical evidence is limited, and the few existing results are contrasting. In addition, while most of the existing trials have been focused on the effects of ALA administration in Alzheimer’s disease (AD) or other types of dementia, studies evaluating its effects on nonclinical elder population are still missing. Methods: In the present open-label, pilot study, fifteen elder patients (mean age: 84.5 ± 5.77) received ALA at a daily dose of 600 mg/day for 12 weeks. General cognitive function, executive function, and mood symptom assessment were carried out at baseline and at the endpoint. Results: Overall, ALA administration was generally well-tolerated (only one dropout due to gastrointestinal side effects). However, no statistically significant effects either on cognitive function, executive function, or mood were found. Conclusions: Despite several limitations, our study found no evidence of positive effects on cognition and mood after ALA administration in elder people without the diagnosis of AD or cognitive impairment. Further clinical trials are needed to better investigate ALA effectiveness on cognition and mood in elder subjects