Neurosurgery
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Parkinson disease (PD) impairs daily functioning for an increasing number of patients and has a growing national economic burden. Deep brain stimulation (DBS) may be the most broadly accepted procedural intervention for PD, but cost-effectiveness has not been established. Moreover, magnetic resonance image-guided focused ultrasound (FUS) is an emerging incisionless, ablative treatment that could potentially be safer and even more cost-effective. ⋯ Bilateral DBS imparts the most utility and cost-effectiveness for PD. If our established success threshold is met, FUS ablation could dominate bilateral DBS's cost-effectiveness from a societal cost perspective.
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Neoplasms of the peripheral nervous system represent a heterogenous group with a wide spectrum of morphological features and biological potential. They range from benign and curable by complete excision (schwannoma and soft tissue perineurioma) to benign but potentially aggressive at the local level (plexiform neurofibroma) to the highly malignant (malignant peripheral nerve sheath tumors [MPNST]). In this review, we discuss the diagnostic and pathologic features of common peripheral nerve sheath tumors, particularly those that may be encountered in the intracranial compartment or in the spine and paraspinal region. ⋯ We also discuss the diagnostic relevance of these neoplasms to specific genetic and familial syndromes of nerve, including neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis. In addition, we discuss updates in our understanding of the molecular alterations that represent key drivers of these neoplasms, including neurofibromatosis type 1 and type 2, SMARCB1, LZTR1, and PRKAR1A loss, as well as the acquisition of CDKN2A/B mutations and alterations in the polycomb repressor complex members (SUZ12 and EED) in the malignant progression to MPNST. In summary, this review covers practical aspects of pathologic diagnosis with updates relevant to neurosurgical practice.
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Accurate circulating biomarkers have potential clinical applications in population screening, tumor subclassification, monitoring tumor status, and the delivery of individualized treatments resulting from tumor genotyping. Recently, significant progress has been made within this field in several cancer types, but despite the many potential benefits, currently there is no validated circulating biomarker test for patients with glioma. ⋯ In the following article, we provide a narrative review of the current evidence pertaining to circulating biomarkers in patients with glioma, including discussion of the advantages and challenges encountered with the current methods used for discovery. Additionally, the potential clinical applications are described with reference to the literature.
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Cerebral cavernous angioma (CA) is a capillary microangiopathy predisposing more than a million Americans to premature risk of brain hemorrhage. CA with recent symptomatic hemorrhage (SH), most likely to re-bleed with serious clinical sequelae, is the primary focus of therapeutic development. Signaling aberrations in CA include proliferative dysangiogenesis, blood-brain barrier hyperpermeability, inflammatory/immune processes, and anticoagulant vascular domain. Plasma levels of molecules reflecting these mechanisms and measures of vascular permeability and iron deposition on magnetic resonance imaging are biomarkers that have been correlated with CA hemorrhage. ⋯ The project tests a novel integrational approach of biomarker development in a mechanistically defined cerebrovascular disease with a relevant context of use, with an approach applicable to other neurological diseases with similar pathobiologic features.
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Review Retracted Publication
"Zooming in" on Glioblastoma: Understanding Tumor Heterogeneity and its Clinical Implications in the Era of Single-Cell Ribonucleic Acid Sequencing.
Glioblastoma (GBM) is the most common primary brain malignancy in adults and one of the most aggressive of all human cancers. It is highly recurrent and treatment-resistant, in large part due to its infiltrative nature and inter- and intratumoral heterogeneity. This heterogeneity entails varying genomic landscapes and cell types within and between tumors and the tumor microenvironment (TME). ⋯ A revolutionary next step forward has been the advent of single-cell RNA sequencing (scRNAseq), which examines gene expression at the single-cell level. scRNAseq has enabled us to understand GBM heterogeneity in unprecedented detail. We review seminal studies in our progression of understanding GBM heterogeneity, with a focus on scRNAseq and the insights that it has provided into understanding the GBM tumor mass, peritumoral space, and TME. We highlight preclinical and clinical implications of this work and consider its potential to impact neuro-oncology and to improve patient outcomes via personalized medicine.