NEURO

Purpose of review This review aims to discuss examples of changes in glucose (sugar) metabolism after traumatic brain injury (TBI). It will attempt to provide an understanding of what changes in glucose metabolism mean for the injured brain. It will further identify potential therapeutic target(s) emanating from our growing understanding of glucose pathways and their roles in TBI. Recent findings Although a significant fraction of glucose is utilized for the energy production in the brain, a small fraction is utilized in other, often ignored pathways. Recent studies have unraveled unexpected biological effects of glucose through these pathways, including redox regulation, genetic and epigenetic regulation, glycation of proteins, nucleotide synthesis and amino acid synthesis. Summary A number of regulatory players in minor glucose metabolic pathways, such as folate and chondroitin sulfate proteoglycans, have recently been identified as potential targets to restore cognitive functions. T

Purpose of review Stroke is a devastating illness which severely attenuates quality of life because of paralysis. Despite recent advances in therapies during acute phase such as thrombolytic therapy, clinical option to intervene the process of rehabilitation is limited. No pharmacological intervention that could enhance the effect of rehabilitation has not been established. Recent articles, which are summarized in the review article, reported novel small compound which accelerates training-dependent motor function recovery after brain damage. Recent findings A novel small compound, edonerpic maleate, binds to collapsin response mediator protein 2 (CRMP2) and enhance synaptic plasticity leading to the acceleration of rehabilitative training-dependent functional recovery after brain damage in rodent and nonhuman primate. The clinical trial to test this effect in human is now ongoing. Future preclinical and clinical studies will delineate the potentials of this compound. Summary A novel C

Purpose of review This review discusses recent advances in the rehabilitation of motor deficits after traumatic brain injury (TBI) and spinal cord injury (SCI) using neuromodulatory techniques. Recent findings Neurorehabilitation is currently the only treatment option for long-term improvement of motor functions that can be offered to patients with TBI or SCI. Major advances have been made in recent years in both preclinical and clinical rehabilitation. Activity-dependent plasticity of neuronal connections and circuits is considered key for successful recovery of motor functions, and great therapeutic potential is attributed to the combination of high-intensity training with electrical neuromodulation. First clinical case reports have demonstrated that repetitive training enabled or enhanced by electrical spinal cord stimulation can yield substantial improvements in motor function. Described achievements include regaining of overground walking capacity, independent standing and steppin

Purpose of review Recent studies on various corticospinal tract (CST) lesions have shown the plastic changes at a variety of motor systems after the lesion. This review provides the alternative routes associated with the motor functional recovery after the CST lesions at various levels in nonhuman primates and rodents. Recent findings In the case of the motor cortical lesions, the perilesional area compensates for the lesion. In contrast, sprouting of the corticoreticular tracts was observed after the lesions involving sensorimotor cortical areas. After the internal capsule lesion, sprouting in the cortico-rubral pathway contributes to the recovery. In case of the pyramidal lesion, rubrospinal and reticulospinal tracts play a role of the functional recovery. After the dorsolateral funiculus (DLF) lesion at C4/C5, the indirect pathway via propriospinal tract contributes to the recovery. In case of the hemisection at lower cervical cord, the CST fibers sprouted from the bilateral motor c

Purpose of review Traumatic brain injury (TBI) represents a major cause of mortality and disability worldwide. In cases of severe TBI, disorders of consciousness (DoC) can occur and therapeutic options for these conditions are few and of limited efficacy. Sensory stimulation, an instrument to improve arousal and awareness, is frequently applied in the neurorehabilitation of DoC, but scientific evidence supporting its efficacy is limited. Our aim is to review the recent literature concerning novel sensory paradigms used in sensory stimulation protocols in DoC following TBI. Recent findings Recent studies on sensory stimulation have investigated different types of stimulation protocols, focusing on the issue of how to demonstrate that improvements are related to the treatment applied and not to spontaneous recovery. Moreover, these studies have also shown that paraclinical tests should be useful not only to discover signs of awareness when behavioural assessment fails to do so, but also

Purpose of review To discuss recent applications of artificial intelligence within the field of neuro-oncology and highlight emerging challenges in integrating artificial intelligence within clinical practice. Recent findings In the field of image analysis, artificial intelligence has shown promise in aiding clinicians with incorporating an increasing amount of data in genomics, detection, diagnosis, classification, risk stratification, prognosis, and treatment response. Artificial intelligence has also been applied in epigenetics, pathology, and natural language processing. Summary Although nascent, applications of artificial intelligence within neuro-oncology show significant promise. Artificial intelligence algorithms will likely improve our understanding of brain tumors and help drive future innovations in neuro-oncology. from Current Opinion in Neurology - Current Issue https://ift.tt/2pGNGLR

Purpose of review The purpose of this review is to discuss how a new treatment modality, tumor treating fields, may be incorporated into the oncologic care for patients with glioblastoma. Recent findings Tumor treating fields are a new treatment modality available to patients with newly diagnosed and recurrent glioblastoma. Alternating electric fields are delivered via a wearable, removable device affixed to the scalp of patients with supratentorial glioblastoma. With continuous use, the application of tumor treating fields combined with temozolomide chemotherapy has been shown to improve overall survival compared with temozolomide alone in patients with newly diagnosed glioblastoma. Adverse events attributable to the device are limited to localized skin reactions. Despite compendium guidelines in support of its use and Food and Drug Administration (FDA) approval, tumor treating fields have been slow to be adopted in the neuro-oncology community. Critics have raised concerns about the

Purpose of review Checkpoint inhibitors (CPIs) represent the forefront of novel immunotherapeutic approaches for the treatment of solid cancers. However, the clinical development of CPIs in glioblastoma (GBM) has been challenging owing to an immunosuppressive tumor microenvironment and, possibly, low tumor mutation burden. Here, we review possible mechanisms responsible for the success of programmed cell death-1 (PD-1) blockade in patients with hypermutated GBM, recent clinical trials of anti-PD-1 monotherapy, trials incorporating neoadjuvant strategies, and trials of immunotherapy combination approaches in GBM. Mechanisms of resistance to immunotherapy and methods to overcome these challenges are also discussed. Recent findings Although two large phase III trials failed to demonstrate the superior efficacy of CPI in comparison with the standard of care in newly diagnosed and recurrent GBM, recent studies suggest that opportunities exist in some patients with GBM. A phase II study show

Purpose of review The current treatment of gliomas dovetails results of decades-old clinical trials with modern trends in chemotherapy. Molecular characterization now plays a pivotal role, and IDH mutations are key characteristics and the subject of active debate. IDH-mutant tumors produce the ‘onco-metabolite’, 2-hydroxyglutarate. Metabolic changes have become central to the understanding of tumor biology, and tumors display a fundamental metabolic change called the Warburg Effect. The Warburg Effect represents a preference for glycolysis, as opposed to oxidative phosphorylation. The present review details the clinical context and discusses clinical and preclinical metabolic imaging tools to characterize the Warburg Effect. Recent findings A clinical Warburg Index is proposed, defined as the lactate concentration measured by 1H-MRSI over the SUV measured by FDG-PET, to measure the Warburg Effect. A preclinical technique called deuterium metabolic imaging has successfully imaged the Wa

Purpose of review Gliomas represent a disparate group of malignancies with varying clinical outcomes despite a tremendous amount of time, effort, and resources dedicated to their management and understanding. The most aggressive entity, glioblastoma, has a dismal prognosis with poor local control despite intense local and systemic treatment, including radiation therapy. Recent findings Given the heterogeneity in genotype, phenotype, and patient outcomes, researchers and clinicians have turned their attention toward attacking DNA damage response and repair mechanisms in gliomas in an effort to develop novel chemo and radiosensitizers. However, despite extensive work in both the laboratory and the clinic, no sensitizers have yet to emerge as clear options in the treatment of glioma, often because of meager preclinical data or an inability to penetrate the blood–brain barrier. Summary This review will examine current understanding of molecular DNA repair targets in glioma and their potent

Purpose of review Primary central nervous system lymphoma (PCNSL) is a rare but aggressive variant of non-Hodgkin lymphoma. The diagnostic gold standard remains the pathologic review of tumor tissue mainly collected though biopsies. The majority of PCNSL are diffuse large B cell lymphoma (DLBCL). Biopsies are invasive procedures, and there have been efforts to develop minimally invasive diagnostic testing using serum and cerebral spinal fluid. This article reviews multiple markers that could potentially serve as future diagnostic tools and predictors of treatment response. Recent findings Many studies have attempted to classify DLBCL into different subtypes for prognostic purposes using methods such as immunohistochemistry. PCNSL often falls under the activated B-cell-like subgroup, and further genomic sequencing has identified alterations in genes within the B-cell receptor signaling axis at increased frequencies. Two such genes, MYD88 and CD79B, implicate the involvement of the NF-kB

Purpose of review Although all primary central nervous system (CNS) tumors are rare, certain tumor types each represent less than 2% of the total and an annual incidence of about 1000 patients or less. Most of them are disproportionally diagnosed in children and young adults, but older adults can also be affected and are rarely recruited to clinical trials. Recent new molecular techniques have led to reclassification of some of these tumors and discovery of actionable molecular alterations. Recent findings We review recent progress in the molecular understanding and therapeutic options of selected rare CNS tumors, with a focus on select clinical trials (temozolomide and lapatinib for recurrent ependymoma; vemurafenib for BRAFV600E-mutated tumors), as well as tumor-agnostic approvals (pembrolizumab, larotrectinib) and their implications for rare CNS tumors. Summary Although rare CNS tumors are a very small fraction of the total of cancers, they represent a formidable challenge. There is

Purpose of review Median survival after the diagnosis of brain metastases has historically been on the order of months. With the recent development of immune checkpoint inhibitors, intracranial activity and durable responses have been observed in brain metastases on multiple phase 2 clinical trials, which have primarily been conducted in patients with melanoma. Immune-related adverse events related to checkpoint inhibitor therapy of brain metastasis can present unique challenges for the clinician and underscore the need for a multidisciplinary team in the care of these patients. The goal of this review is to address the current knowledge, limitations of understanding, and future directions in research regarding immune therapy trials and neurologic toxicities based on retrospective, prospective, and case studies. Recent findings Immune therapy has the potential to exacerbate symptomatic edema and increase the risk of radiation necrosis in previously irradiated lesions. Neurologic toxici

Purpose of review Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common and distressing side-effect of many chemotherapy regimens. Currently, aside from symptomatic treatments for neuropathic pain, there are no treatments to prevent CIPN or treat established CIPN. We discuss recent articles addressing clinimetric issues and treatment of CIPN. Recent findings There are important clinimetric issues that need to be addressed so that robust clinical trials in CIPN can be performed. There are new compounds in early development that may treat CIPN, but larger studies are needed. Summary A multidisciplinary, international approach is needed to unravel CIPN; the Toxic Neuropathy Consortium (TNC) of the Peripheral Nerve Society may be the home for such efforts. from Current Opinion in Neurology - Current Issue https://ift.tt/2L1TqYD

Purpose of review Single-organ vasculitis of the peripheral nervous system (PNS) is often designated nonsystemic vasculitic neuropathy (NSVN). Several variants or subtypes have been distinguished, including migratory sensory neuropathy, postsurgical inflammatory neuropathy, diabetic radiculoplexus neuropathies, skin-nerve vasculitides, and, arguably, neuralgic amyotrophy. NSVN often presents as nondiabetic lumbosacral radiculoplexus neuropathy (LRPN). This review updates classification, clinical features, epidemiology, and imaging of these disorders. Recent findings A recent study showed the annual incidence of LRPN in Olmstead County, Minnesota to be 4.16/100 000:2.79/100 000 diabetic and 1.27/100 000 nondiabetic. This study was the first to determine the incidence or prevalence of any vasculitic neuropathy. In NSVN, ultrasonography shows multifocal enlargement of proximal and distal nerves. In neuralgic amyotrophy, MRI and ultrasound reveal multifocal enlargements and focal constrict

Purpose of review Congenital myasthenic syndromes (CMS) are a group of heterogeneous inherited disorders caused by mutations in genes encoding proteins whose function is essential for the integrity of neuromuscular transmission. This review updates the reader on the expanding phenotypic spectrum and suggested improved treatment strategies. Recent findings As next-generation sequencing is taken into the clinic, its use is both continuing to unearth new causative genes in which mutations underlie CMS and also broadening the phenotypic spectrum for known CMS genes. The number of genes in which mutations may cause neuromuscular transmission defects has now passed 30. The defective transmission may be part of an overall more complex phenotype in which there may be muscle, central nervous system or other involvement. Notably, mutations in series of genes encoding proteins located in the presynatic motor bouton have been identified. Rare cases of mutations in basal laminar proteins of the syn

Purpose of review Idiopathic inflammatory myopathies (IIM) are rare diseases with heterogenous clinicopathological features. In recent years, new classification systems considering various combinations of clinical, serological, and pathological information have been proposed. This review summarizes recent clinicoseropathological development in major subgroups of IIM. Recent findings Considering clinicoseropathological features, IIM are suggestively classified into four major subgroups: dermatomyositis, immune-mediated necrotizing myopathy (IMNM), antisynthetase syndrome (ASS), and inclusion body myositis (IBM). Many historically diagnosed polymyositis have been mainly reclassified as IBM, IMNM, and ASS. Different types of myositis-specific antibodies (MSA) suggest distinct clinicopathological subsets of IIM. Excluding IBM, at least one-third of the IIMs have no known associated MSA. Summary MSA are crucial for IIM classification but can be negative. Thus, IIM should be universally clas

Purpose of review Although mitochondrial diseases impose a significant functional limitation in the lives of patients, treatment of these conditions has been limited to dietary supplements, exercise, and physical therapy. In the past few years, however, translational medicine has identified potential therapies for these patients. Recent findings For patients with primary mitochondrial myopathies, preliminary phase I and II multicenter clinical trials of elamipretide indicate safety and suggest improvement in 6-min walk test (6MWT) performance and fatigue scales. In addition, for thymidine kinase 2-deficient (TK2d) myopathy, compassionate-use oral administration of pyrimidine deoxynucleosides have shown preliminary evidence of safety and efficacy in survival of early onset patients and motor functions relative to historical TK2d controls. Summary The prospects of effective therapies that improve the quality of life for patients with mitochondrial myopathy underscore the necessity for de

Purpose of review The purpose of this review is to highlight updates in the standard of care recommendations for DMD, and to describe approaches to and recent advances in genetic therapies for DMD. Recent findings Treatment of DMD patients with the corticosteroids prednisone or deflazacort remains the standard of care, and recent data shows that early treatment (as young as 5 months) with a weekend dosing regimen results in measurable improvement in motor outcomes. A mutation-specific therapy directed at restoring an open reading frame by skipping exon 51 is FDA-approved, and therapies directed at other exons are in trials. Gene replacement therapy shows significant promise in animal models, and trials are underway. Genome editing has received significant attention because of results in animal models, but challenges to implementation in humans remain. Summary The mainstay of treatment remains meeting well defined standards of care that have been shown to influence morbidity and mortali

Purpose of review Emery–Dreifuss muscular dystrophy (EDMD) is caused by mutations in EMD encoding emerin and LMNA encoding A-type lamins, proteins of the nuclear envelope. In the past decade, there has been an extraordinary burst of research on the nuclear envelope. Discoveries resulting from this basic research have implications for better understanding the pathogenesis and developing treatments for EDMD. Recent findings Recent clinical research has confirmed that EDMD is one of several overlapping skeletal muscle phenotypes that can result from mutations in EMD and LMNA with dilated cardiomyopathy as a common feature. Basic research on the nuclear envelope has provided new insights into how A-type lamins and emerin function in force transmission throughout the cell, which may be particularly important in striated muscle. Much of the recent research has focused on the heart and LMNA mutations. Prevalence and outcome studies have confirmed the relative severity of cardiac disease. Robu