scholarly journals Controversial roles for dexamethasone in glioblastoma – Opportunities for novel vascular targeting therapies

2019 ◽  
Vol 39 (8) ◽  
pp. 1460-1468 ◽  
Author(s):  
Daniel Dubinski ◽  
Elke Hattingen ◽  
Christian Senft ◽  
Volker Seifert ◽  
Kevin G Peters ◽  
...  
Keyword(s):  
Neurological Impairment ◽  
Primary Brain Tumor ◽  
Vascular Targeting ◽  
Clinical Approach ◽  
Major Contributor ◽  
Treatment Resistant ◽  
Alternative Strategies ◽  
Macula Edema ◽  
Clinical Level ◽  
Metastasis Therapy

Glioblastoma is a highly aggressive and treatment resistant primary brain tumor. Features of glioblastoma include peritumoral cerebral edema, the major contributor to neurological impairment. Although the current clinical approach to edema management is administration of the synthetic corticoid dexamethasone, increasing evidence indicates numerous adverse effects of dexamethasone on glioblastoma burden at the molecular, cellular and clinical level. The contradictions of dexamethasone for glioblastoma and brain metastasis therapy are discussed in this article. Finally, alternative strategies for cerebrovascular edema therapy with vascular stabilizing, anti-permeability agents that are either approved or in clinical trials for diabetic retinopathy and macula edema, are addressed.

scholarly journals The Interplay between Glioblastoma and Its Microenvironment

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2257
Author(s):  
Mark Dapash ◽  
David Hou ◽  
Brandyn Castro ◽  
Catalina Lee-Chang ◽  
Maciej S. Lesniak
Keyword(s):  
Tumor Microenvironment ◽  
Patient Outcomes ◽  
Poor Prognosis ◽  
Primary Brain Tumor ◽  
Major Contributor ◽  
Complex Interplay ◽  
Environmental Pressures ◽  
The Poor ◽  
Adaptive Nature ◽  
Poor Efficacy

GBM is the most common primary brain tumor in adults, and the aggressive nature of this tumor contributes to its extremely poor prognosis. Over the years, the heterogeneous and adaptive nature of GBM has been highlighted as a major contributor to the poor efficacy of many treatments including various immunotherapies. The major challenge lies in understanding and manipulating the complex interplay among the different components within the tumor microenvironment (TME). This interplay varies not only by the type of cells interacting but also by their spatial distribution with the TME. This review highlights the various immune and non-immune components of the tumor microenvironment and their consequences f the efficacy of immunotherapies. Understanding the independent and interdependent aspects of the various sub-populations encapsulated by the immune and non-immune components will allow for more targeted therapies. Meanwhile, understanding how the TME creates and responds to different environmental pressures such as hypoxia may allow for other multimodal approaches in the treatment of GBM. Ultimately, a better understanding of the GBM TME will aid in the development and advancement of more effective treatments and in improving patient outcomes.

Central pain syndromes

2020 ◽  
Vol 47 (3) ◽  
pp. 285-297
Author(s):  
Deena Hassaballa ◽  
Richard L. Harvey
Keyword(s):  
Signs And Symptoms ◽  
Neurological Impairment ◽  
Clinical Approach ◽  
Central Pain ◽  
Holistic View ◽  
Pain Syndromes ◽  
Cord Injury ◽  
Assessment And Treatment ◽  
Neurological Injuries

The management of pain in persons with neurological injuries is challenging and complex. A holistic view and clinical approach are necessary when addressing pain in patients with neurological impairment because interpreting signs and symptoms and deciphering sources of pain is never a straightforward process. This problem is further magnified with the management of central pain syndromes. The best approach is to have a good understanding of the clinical characteristics commonly found in this patient population, in particular for patients with stroke, multiple sclerosis (MS), or spinal cord injury (SCI), as central pain manifests differently between these groups. This paper will focus on the history, clinical presentation, pathophysiology, assessment, and treatment of central pain in patients with these types of neurological conditions. In addition to being at risk for a decline in quality of life, patients with pain syndromes are also prone to adverse responses to treatments (e.g., opioid addiction). It is therefore important to methodically analyze the similarities and differences between patients with different pain syndromes.

scholarly journals Gut Microbiota in Depression: A Focus on Ketamine

2021 ◽  
Vol 15 ◽  
Author(s):  
Alina Wilkowska ◽  
Łukasz Piotr Szałach ◽  
Wiesław Jerzy Cubała
Keyword(s):  
Gut Microbiota ◽  
Treatment Strategies ◽  
Antidepressant Effect ◽  
Global Burden ◽  
Major Contributor ◽  
Treatment Resistant ◽  
Major Depressive ◽  
Animal Models Of Depression ◽  
Treatment Of Depression

According to the WHO, major depressive disorder is the leading cause of disability worldwide, and it is a major contributor to the overall global burden of disease. The pathophysiology of this common and chronic disease is still not completely understood. The gut microbiome is an increasingly recognized environmental factor that can have a role in depression, acting through the gut–microbiota–brain axis. The available treatment for depression is still insufficient since 30% of patients are treatment-resistant. There is an unquestionable need for novel strategies. Ketamine is an effective antidepressant in treatment-resistant patients. It is suggested that the antidepressant effect of ketamine may be partially mediated by the modification of gut microbiota. In this study, we presented a review of data on gut microbiota in depression with special attention to the effect of ketamine on the microbiome in animal models of depression. Earlier reports are preliminary and are still insufficient to draw firm conclusion, but further studies in this field might help to understand the role of the gut–brain axis in the treatment of depression and might be the ground for developing new effective treatment strategies.

Central Nerve System Impairment, AMA Guides, Sixth Edition: An Overview

2018 ◽  
Vol 23 (1) ◽  
pp. 10-13
Author(s):  
James B. Talmage ◽  
Jay Blaisdell
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Neurological Impairment ◽  
Sixth Edition ◽  
Central Nerve System ◽  
The Central Nervous System ◽  
The One ◽  
Nerve System ◽  
The Brain

Abstract Injuries that affect the central nervous system (CNS) can be catastrophic because they involve the brain or spinal cord, and determining the underlying clinical cause of impairment is essential in using the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), in part because the AMA Guides addresses neurological impairment in several chapters. Unlike the musculoskeletal chapters, Chapter 13, The Central and Peripheral Nervous System, does not use grades, grade modifiers, and a net adjustment formula; rather the chapter uses an approach that is similar to that in prior editions of the AMA Guides. The following steps can be used to perform a CNS rating: 1) evaluate all four major categories of cerebral impairment, and choose the one that is most severe; 2) rate the single most severe cerebral impairment of the four major categories; 3) rate all other impairments that are due to neurogenic problems; and 4) combine the rating of the single most severe category of cerebral impairment with the ratings of all other impairments. Because some neurological dysfunctions are rated elsewhere in the AMA Guides, Sixth Edition, the evaluator may consult Table 13-1 to verify the appropriate chapter to use.

Impairment Tutorial: Neurological Impairment Evaluation: Overview of Sixth Edition Approaches

2008 ◽  
Vol 13 (2) ◽  
pp. 6-8
Author(s):  
Lorne Direnfeld ◽  
Christopher R. Brigham ◽  
Elizabeth Genovese
Keyword(s):  
Spinal Cord ◽  
Neurological Impairment ◽  
Diagnostic Techniques ◽  
Neurological Deficits ◽  
Sixth Edition ◽  
Pain Disability ◽  
Whole Person ◽  
Disability Questionnaire ◽  
Cervical Plating

Abstract The AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), does not provide a Diagnosis-based estimate of impairment due to syringomyelia, a disorder in which a cyst (syrinx), develops within the central spinal cord and destroys neural tissue as it expands. The AMA Guides, however, does provide an approach to rating a syringomyelia based on objective findings of neurological deficits identified during a neurological examination and demonstrated by standard diagnostic techniques. Syringomelia may occur after spinal cord trauma, including a contusion of the cord. A case study illustrates the rating process: The case patient is a 46-year-old male who fell backwards, landing on his upper back and head; over a five-year period he received a T5-6 laminectomy and later partial corpectomies of C5, C6, and C7, cervical discectomy C5-6 and C6-7; iliac crest strut graft fusion of C5-6 and C6-7; and anterior cervical plating of C5 to C7 for treatment of myelopathy; postoperatively, the patient developed dysphagia. The evaluating physician should determine which conditions are ratable, rate each of these components, and combine the resulting whole person impairments without omission or duplication of a ratable impairment. The article includes a pain disability questionnaire that can be used in conjunction with evaluations conducted according to Chapter 3, Pain, and Chapter 17, The Spine.

Interhemispheric transfer evaluation in multiple sclerosis 1The authors would like to thank Claude-Alain Hauert and Christoph Michel for their assistance in the evaluation of motor tapping and Michel Habib for his suggestions and comments. This work was supported by a grant from the Swiss Society of Multiple Sclerosis.

2000 ◽  
Vol 59 (3) ◽  
pp. 150-158 ◽  
Author(s):  
Nadia Ortiz ◽  
Michael Reicherts ◽  
Alan J. Pegna ◽  
Encarni Garran ◽  
Michel Chofflon ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Corpus Callosum ◽  
Lexical Decision ◽  
Dichotic Listening ◽  
Neurological Impairment ◽  
Interhemispheric Transfer ◽  
Decision Task ◽  
Swiss Society ◽  
Listening Test ◽  
Relapsing Remitting

Patients suffering from Multiple Sclerosis (MS) have frequently been found to suffer from damage to callosal fibers. Investigations have shown that this damage is associated with signs of hemisphere disconnections. The aim of our study was to provide evidence for the first signs of interhemispheric dysfunction in a mildly disabled MS population. Therefore, we explored whether the Interhemispheric Transfer (IT) deficit is multi-modal and sought to differentiate two MS evolution forms, on the basis of an interhemispheric disconnection index. Twenty-two patients with relapsing-remitting form of MS (RRMS) and 14 chronic-progressive (CPMS) were compared with matched controls on four tasks: a tachistoscopic verbal and non-verbal decision task, a dichotic listening test, cross tactile finger localization and motor tapping. No overall impairment was seen. The dichotic listening and lexical decision tasks were the most sensitive to MS. In addition, CPMS patients' IT was more impaired and was related to the severity of neurological impairment. The different sizes of the callosal fibers, which determine their vulnerability, may explain the heterogeneity of transfer through the Corpus Callosum. Therefore, evaluation of IT may be of value as an index of evolution in MS.

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