Showing papers in "Expert Review of Neurotherapeutics in 2018"
TL;DR: The hypothesis that intestinal microbiota may help protect against AD, in part, by supporting the generation of select SCFAs, which interfere with the formation of toxic soluble Aβ aggregates is supported.
Abstract: Background: Dietary fibers are metabolized by gastrointestinal (GI) bacteria into short-chain fatty acids (SCFAs). We investigated the potential role of these SCFAs in β-amyloid (Aβ) mediated pathological processes that play key roles in Alzheimer’s disease (AD) pathogenesis.Research design and methods: Multiple complementary assays were used to investigate individual SCFAs for their dose-responsive effects in interfering with the assembly of Aβs1-40 and Aβ1-42 peptides into soluble neurotoxic Aβ aggregates.Results: We found that several select SCFAs are capable of potently inhibiting Aβ aggregations, in vitro.Conclusion: Our studies support the hypothesis that intestinal microbiota may help protect against AD, in part, by supporting the generation of select SCFAs, which interfere with the formation of toxic soluble Aβ aggregates.
215 citations
TL;DR: The most problematic cases include skull base meningiomas that enclose vasculo-nervous structures and surgery- and radiation-refractory tumors that present with significant morbidity and mortality.
Abstract: With an annual incidence of 5/100,000, meningioma is the most frequent primary tumor of the central nervous system. Risk factors are radiotherapy and hormone intake. Most meningiomas are grade I benign tumors, but up to 15% are atypical and 2% anaplastic according to the WHO 2016 histological criteria. Areas covered: This review details the current standard therapy based on international guidelines and recent literature, and describes new approaches developed to treat refractory cases. First-line treatments are observation and surgery, but adjuvant radiotherapy/radiosurgery is discussed for atypical and indicated for anaplastic meningiomas. The most problematic cases include skull base meningiomas that enclose vasculo-nervous structures and surgery- and radiation-refractory tumors that present with significant morbidity and mortality. The treatment of recurrent tumors is based on radiotherapy and repeated surgery. Systematic therapies are not effective in general but several clinical trials are ongoing. Expert commentary: Molecular characterization of the tumors, based on genetic mutations such as NF2, SMO, TERT, TRAF7, and on the methylation profile are developing, completing the histological classification and giving new insights into prognosis and treatment options.
139 citations
TL;DR: There is great need for clinical trials to evaluate new antioxidant compounds specifically on epileptic patients, and definitive evidence about the neuroprotective ability of the existing compounds is still lacking.
Abstract: The brain is particularly susceptible to oxidative stress being the most aerobically active organ in the body due to its high metabolic demands. It also contains high concentrations of polyunsaturated fatty acids that are prone to lipid peroxidation and is rich in iron which can catalyze hydroxyl radical formation. There is evidence that neuronal hyperexcitability and oxidative injury produced by an excessive production of free radicals may play a role in the initiation and progression of epilepsy. Epilepsy is one of the most common neurological disorders and may provoke serious physical, psychological, socioeconomic consequences. Understanding the role of oxidative stress in the pathophysiology of seizures is essential to delineate appropriate therapeutic strategies. Compounds with neuroprotective or antioxidant function may exert positive effects when associated with antiepileptic drugs (AEDs). The latter themselves may play a role of antioxidants or neuroprotectants. In fact, most AEDs currently in use have been tested for a possible neuroprotective ability both in human and animal models of epilepsy.
107 citations
TL;DR: Internet-supported and therapist-guided cognitive behaviour therapy (ICBT) is effective for a range of problems in the short run, but less is known about the long-term effects with follow-ups of two years or longer.
Abstract: Introduction: Internet-supported and therapist-guided cognitive behaviour therapy (ICBT) is effective for a range of problems in the short run, but less is known about the long-term effects with fo ...
72 citations
TL;DR: The future direction of VS management lies in obtaining longer-term follow-up data for patients with treated VS, and in improved understanding of cellular pathways and targeted therapies.
Abstract: Introduction: Vestibular schwannomas (VS) account for approximately 85% of tumors in the cerebello-pontine angle, with a lifetime incidence of approximately 1 in 1000. Most are sporadic, with appro...
66 citations
TL;DR: The EXIST-3 trial provided the first evaluation of the optimal dosage, conferring a higher chance of reducing seizure frequency and severity, with adverse events being similar to what observed with lower dosages.
Abstract: Introduction. The mammalian target of rapamycin (mTOR) pathway has emerged as a key player for proper neural network development, and it is involved in epileptogenesis triggered by both genetic or ...
66 citations
TL;DR: The evidence showing low-grade inflammation in mood disorders and the studies evaluating immune-based strategies for the treatment of these conditions are reviewed.
Abstract: Introduction: Inflammation seems to play a role in the pathophysiology of mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD). In the last years several studies have...
66 citations
TL;DR: A comprehensive review of BACE inhibitors for AD treatment is provided, focusing on the most advanced compounds in Phase III RCTs, and indicates that blocking the formation of nascent Aβ is not useful in AD.
Abstract: Introduction: The amyloid hypothesis of Alzheimer’s disease (AD) affirms that brain accumulation of amyloid-β (Aβ) oligomers and soluble aggregates represent the major pathological event of the dis...
58 citations
TL;DR: This paper reviews the literature describing the association between incident stroke and sleep apnea, rapid eye movement sleep behavior disorder, restless legs syndrome, periodic limb movements of sleep, insomnia, and shift work and identifies novel targets for stroke prevention.
Abstract: Introduction: Stroke is a major cause of disability and death in the United States and across the world, and the incidence and prevalence of stroke are expected to rise significantly due to an aging population. Obstructive sleep apnea, an established independent risk factor for stroke, is a highly prevalent disease that is estimated to double the risk of stroke. It remains uncertain whether non-apnea sleep disorders increase the risk of stroke.Areas covered: This paper reviews the literature describing the association between incident stroke and sleep apnea, rapid eye movement sleep behavior disorder, restless legs syndrome, periodic limb movements of sleep, insomnia, and shift work.Expert commentary: Trials of continuous positive airway pressure for stroke prevention in sleep apnea patients have been largely disappointing, but additional trials that target populations not yet optimally studied are needed. Self-reported short and long sleep duration may be associated with incident stroke. However,...
44 citations
TL;DR: State-of-the-art neuroimaging techniques provide fundamental instruments for the detection and quantification of upper motor neuron and extra-motor brain involvement in ALS, with relevance for both pathophysiologic investigation and clinical practice.
Abstract: Introduction: Several neuroimaging techniques have been used to define in vivo markers of pathological alterations underlying amyotrophic lateral sclerosis (ALS). Growing evidence supports the use ...
43 citations
TL;DR: This review summarizes the own experience and published evidence in the treatment of chorea, defined as jerk-like movements that move randomly from one body part to another, as well as evaluating current guidelines and clinical practices for chorea of all etiologies.
Abstract: Introduction: Chorea is defined as jerk-like movements that move randomly from one body part to another. It is due to a variety of disorders and although current symptomatic therapy is quite effect...
TL;DR: Neurocysticercosis is a neglected disease that contributes substantially to neurological morbidity/mortality in lower-income countries and increasingly among high- income countries due to migration, but strategies to eradicate NC must be created with the involvement of all stakeholders.
Abstract: Introduction: Neurocysticercosis (NC) is a neglected disease that contributes substantially to neurological morbidity/mortality in lower-income countries and increasingly among high-income countrie...
TL;DR: There has been an increased effort to develop symptom-specific treatments in MS that directly target mobility disability; however, more research is needed to determine the efficacy of these rehabilitative strategies alone and together for improving walking in persons with MS.
Abstract: INTRODUCTION Mobility disability is one of the most widespread and impactful consequences of multiple sclerosis (MS). Disease modifying drugs (DMDs) may delay the progression of disability over time; however, there is minimal evidence supporting the efficacy of DMDs for reversing mobility disability or restoring ambulatory function in persons with MS. Areas covered: This review outlines symptomatic pharmacologic and non-pharmacologic therapeutic approaches that target mobility disability with the goal of restoring and improving walking function. First, the efficacy of dalfampridine, currently the only Food and Drug Administration approved symptomatic pharmacologic agent that improves walking in persons with MS is described. Next, a review of the efficacy of non-pharmacologic therapies for improving walking, including exercise training, physical therapy, and gait training is given. Last, guidance on future research on mobility in MS is provided by emphasizing the importance of combinatory treatment approaches that include multiple intervention modalities, as the best treatment plan likely involves a comprehensive, multidisciplinary approach. Expert commentary: There has been an increased effort to develop symptom-specific treatments in MS that directly target mobility disability; however, more research is needed to determine the efficacy of these rehabilitative strategies alone and together for improving walking in persons with MS.
TL;DR: Early clinical experience and expert opinion suggest that utilization of COM technologies such as the PKG have the potential to improve medical care in people with PD.
Abstract: Introduction: Evaluation of people with Parkinson’s disease (PD) is often complex due to heterogeneity of symptoms and disease course, including the variability of motor fluctuations and dyskinesia...
TL;DR: The great interest in development of treatments specific for MG is welcome, but decisions will need to be made to focus on those that offer significant benefits to patients.
Abstract: Introduction: Myasthenia gravis (MG) is an autoimmune neuromuscular disorder with no cure and conventional treatments limited by significant adverse effects and variable benefit. In the last decade...
TL;DR: This work states that reliable prevalence rates of conditions associated with stigma can better be assessed if acquainted field personnel conduct the interviews, and accurate diagnosis of most noncommunicable neurological diseases requires the use of sophisticated technology that is not available in these areas.
Abstract: Owing to increased life expectancy and changes in lifestyles, the burden of noncommunicable neurological diseases is on the rise in rural areas of developing countries, to the point of being consid...
TL;DR: These are recent advances in assessment and therapy of chronic tic disorders, encompassing the three stages of intervention, with the addition of experimental, non-invasive brain stimulation strategies.
Abstract: Introduction: The management of Tourette syndrome (TS) and other chronic tic disorders occurs in multiple stages and begins with comprehensive assessment and complex psychoeducation. Behavioral and pharmacological interventions (second stage) are needed when tics cause physical or psychosocial impairment. Deep brain stimulation surgery or experimental therapies represent the third stage.Areas covered: Discussed are recent advances in assessment and therapy of chronic tic disorders, encompassing the three stages of intervention, with the addition of experimental, non-invasive brain stimulation strategies. A PubMed search was performed using as keywords: ‘tic disorders’, ‘Tourette syndrome’, ‘assessment’, ‘rating scales’, ‘behavioral treatment’, ‘pharmacological treatment’, ‘deep brain stimulation’, ‘transcranial magnetic (or current) stimulation’, and ‘transcranial current stimulation’. More than 300 peer-reviewed articles were evaluated. The studies discussed have been selected on the basis of nov...
TL;DR: A literature search was conducted using MEDLINE on the topics of imaging, biomarkers, ICH prevention and treatment trials in CAA, focusing on its current diagnosis and management and opportunities for future therapeutic approaches.
Abstract: Introduction: Cerebral amyloid angiopathy (CAA) is characterized by the pathologic deposition of amyloid-beta within cortical and leptomeningeal arteries, arterioles, capillaries and, in rare cases...
TL;DR: The impact on quality of life appeared most promising in care home settings, and individual approaches were associated with improved cognition and mood and group approaches were linked to improved communication.
Abstract: Introduction: Reminiscence therapy (RT) is a popular psychosocial intervention widely used in dementia care. It involves discussion of past events and experiences, using tangible prompts to evoke m...
TL;DR: The main research questions at this time are: the Relative safety, efficacy, and expense of DBS, SRS, and FUS performed unilaterally and bilaterally; the relative safety and efficacy of thalamic versus subthalamic targeting; the need for intraoperative microElectrode recordings and macroelectrode stimulation in awake patients to identify the optimum anatomical target.
Abstract: Introduction: Essential tremor is the most common form of pathologic tremor. Surgical therapies disrupt tremorogenic oscillation in the cerebellothalamocortical pathway and are capable of abolishin...
TL;DR: In the absence of objective in vivo biomarkers for quantitative standardized information, scale-based clinical gradation systems provide a suitable alternative for gradation of PD manifestations severity.
Abstract: Introduction: Parkinson’s disease (PD) is expressed through motor and non-motor symptoms (NMS) that differ considerably in presence and severity among patients and over time. Furthermore, the progression pattern of the NMS does not necessarily parallel the course of the motor impairment. Gradation of PD according to the motor impairment and burden of NMS is an unmet need for an appropriate management of patients.Areas covered: A review of the studies on clinical gradation methods applied to PD is carried out in this article. Studies have provided cut-off values for a pragmatic classification of scores from rating scales and questionnaires in mild, moderate, and severe PD, considering motor state, complications, disability, and NMS. Grading systems with Hoehn and Yahr staging, Clinical Impression of Severity Index for PD, NMS Scale, NMS Questionnaire, and MDS-UPDRS, are available. These systems are reviewed in detail and examples in format of simple cards are presented.Expert commentary: Patients c...
TL;DR: This review aims to explore TAM targeting in GBM as a promising therapeutic option in the near future after finding that interactions between TAM and GBM cells promote tumor oncogenesis.
Abstract: Introduction: Glioblastoma (GBM) is the deadliest primary malignant central nervous system (CNS) tumor with a median overall survival of 15 months despite a very intensive therapeutic regim...
TL;DR: GPi-DBS is effective and safe in isolated dystonia and should not be delayed when symptoms compromise quality of life and functionality, and evidence suggests that younger patients with shorter disease duration experience greater benefit following DBS.
Abstract: Introduction: Treatment of dystonia should be individualized and tailored to the specific needs of patients. Surgical treatment is an important option in medically refractory cases. Several issues ...
TL;DR: A Gold Standard of Care is suggested which healthcare professionals and services should aim for when approaching SUDEP risk management and a Minimum Standard of care is proposed that is practical to implement, that all people with epilepsy should expect to receive.
Abstract: Introduction: Sudden Unexpected Death in Epilepsy (SUDEP) is a significant cause of death for people with chronic epilepsy. Good practice guidance in the UK and the USA expect SUDEP to be discussed...
TL;DR: Increased awareness of the benefits of surgery, growing surgical experience, broadening of indications, and improved imaging and source localization techniques have all led to an earlier referral pattern of children for surgical evaluation, and to a significantly increased number of pediatric surgeries, but epilepsy surgery remains an underutilized treatment for children with epilepsy.
Abstract: Epilepsy surgery is the only curative treatment currently available for focal lesional pharmacoresistant epilepsy. New antiepileptic drugs (AEDs), the ketogenic diet, or vagal nerve stimulation eac...
TL;DR: Through an improved understanding of the role of autonomic changes in pathogenesis of migraine, it may be possible to develop even more effective treatments for migraine sufferers.
Abstract: Introduction: Migraine is a common complex neurological disorder involving multiple brain areas that regulate autonomic, affective, cognitive, and sensory functions. This review explores autonomic ...
TL;DR: Estriol therapy in two phase 2 trials showed a decrease in clinical disease activity and inflammatory parameters in MRI, however, evidence of a therapeutic effect of testosterone is scarce and these hormones should be considered as an adjunctive therapy.
Abstract: Introduction: Neuroprotection and remyelination are two unmet needs in the treatment of multiple sclerosis (MS). Therapeutic potential has been identified with sexual hormones, supported in women b...
TL;DR: Critical unmet needs for the Integration of TOMs into clinical and research practice are the identification and validation of relevant endpoints for individual patients, the capture of motor and nonmotor activities from an ecologically valid environment, the integration of various sensor data into an open-access, common-language platforms, and the definition of a regulatory pathway for approval of Toms.
Abstract: Introduction: The increasing development and availability of portable and wearable technologies is rapidly expanding the field of technology-based objective measures (TOMs) in neurological disorder...
TL;DR: An extended diagnostic work up in cases with rapidly progressing dementia should include the search for neoplasia as well as atypical encephalitis, and high-dose steroid therapy should be considered in certain clinical situations even when no evidence for inflammation is present.
Abstract: Introduction: Rapidly progressive dementia is a syndrome caused by numerous disease entities Accurate diagnosis is crucial as substantial proportion of these diseases is highly treatable Others m
TL;DR: The review presents an update of the clinical phenotypes and diagnostic options for LGMD including both dominant and recessive LGMD and consider their differential clinical and histopathological features.
Abstract: Introduction: Limb-girdle muscular dystrophies (LGMDs) encompass a clinically heterogeneous group of rare, genetic progressive muscle disorders presenting with weakness and atrophy of predominant p...