NEURO

Purpose of review To give an update on recent imaging studies probing positron emission tomography (PET) as a tool for improving biomarker-guided diagnosis of neuropsychiatric disorders. Recent findings Several studies confirmed the value of imaging of regional neuronal activity and imaging of dopaminergic, serotonergic, and other neuroreceptor function in the diagnostic process of neuropsychiatric disorders, particularly schizophrenia, depression/bipolar disorder, substance use disorders, obsessive compulsive disorders (OCD), and attention-deficit/hyperactivity disorder. Additionally, imaging brain microglial activation using translocator protein 18 kDa (TSPO) radiotracer allows for unique in-vivo insights into pathophysiological neuroinflammatory changes underlying schizophrenia, affective disorders, and OCD. Summary The role of PET imaging in the biomarker-guided diagnostic process of neuropsychiatric disorders has been increasingly acknowledged in recent years. Future prospective s

Purpose of review To give an update on recent findings concerning the use of PET for differential diagnosis in neurodegenerative and neuroinflammatory disorders manifesting on a behavioural level. Recent findings Although accurate differential diagnosis of dementia can be achieved by imaging disease-specific patterns of cerebral glucose metabolism with [18F]fluorodeoxyglucose ([18F]FDG)-PET, the diagnostic impact of [18F]FDG-PET in primary psychiatric disorders is limited. Amyloid-beta PET provides an incremental value beyond [18F]FDG-PET in the differential diagnosis of dementia and was proposed as a biomarker defining the so-called Alzheimer continuum. Recently developed tau-specific tracers might also aid in the diagnostic process (biological definition of Alzheimer's disease together with amyloid-beta). Surpassing the diagnostic accuracy of other techniques, such as MRI, [18F]FDG-PET has also gained widespread clinical use for diagnosis and follow-up of paraneoplastic and autoi

Purpose of review The goal of our nation-wide initiative is to provide clinicians intuitive and robust tools for accurate diagnosis, therapy monitoring and prognosis of cognitive decline that is based on large-scale multidomain data. Recent findings We describe a federation framework that allows for statistical analysis of aggregated brain imaging and clinical phenotyping data across memory clinics in Switzerland. The adaptation and deployment of readily available data capturing and federation modules is paralleled by developments in ontology, quality and regulatory control of brain imaging data. Our initiative incentivizes data sharing through the common resource in a way that provides individual researcher with access to large-scale data that surpasses the data acquisition capacity of a single centre. Clinicians benefit from fine-grained epidemiological characterization of own data compared with the rest additional to intuitive tools allowing for computer-based diagnosis of dementia.

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Purpose of review To summarize the current state of art of gene therapy for Parkinson's disease. Recent findings Introduction of the gene for glutamic acid decarboxylase (GAD) into the subthalamic nucleus was successful in a randomized, double-blind clinical trial and recent data from PET imaging identified novel brain networks underlying both sham surgery and therapeutic responses in treated participants. Two other approaches use viral vectors to increase dopamine transmission in the striatum. Both strategies are being studied in active trials and have recently reported promising responses in human participants. New strategies in Parkinson's disease are focused upon targeting the underlying pathogenesis in those with genetic defects thought to be the cause of disease. Finally, noninvasive focused ultrasound is currently being tested for lesioning in Parkinson's disease patients, but this same technology can be used to transiently open the blood–brain barrier, raising the p

Purpose of review In the last 7 years, changes in five genes [SLC20A2, PDGFRB, PDGFB, XPR1, and MYORG] have been implicated in the pathogenesis of primary familial brain calcification (PFBC), allowing for genetic delineation of this phenotypically complex neurodegenerative disorder. This review explores how the ensuing plethora of reported PFBC patients and their disease-causing variants improved our understanding of disease, pathogenesis, clinical manifestation, and penetrance. Recent findings In PFBC patients, pathogenic changes have been most frequently described in SLC20A2, accounting for approximately the same number of patients as the variants in the other four PFBC genes combined. There is no appreciable relationship between any combination of the following three variables: the type of disease-causing change, the pattern or extent of calcifications, and the presence or nature of clinical manifestation in PFBC patients. Nevertheless, elucidation of underlying genetic factors prov

Purpose of review In this review, we discuss the most recent evidence on mechanisms underlying pathological nociceptive processing in Parkinson's disease patients, as well as novel treatment strategies. Recent findings In Parkinson's disease, specific neurodegenerative changes may cause alterations in nociceptive processing at multiple levels. Optimization of dopaminergic therapies should always be the first step in the management of Parkinson's disease pain. Reportedly, rotigotine transdermal patch, a monoamine oxidase type B inhibitor safinamide (as an add-on therapy to levodopa), subcutaneous apomorphine and intrajejunal levodopa infusion therapy may have a beneficial effect on pain sensations in Parkinson's disease patients. Among the nondopaminergic pharmacological therapies, prolonged-release oxycodone/naloxone and duloxetine may be effective in the treatment of chronic pain in Parkinson's disease. Botulinum toxin (BTX) injections should be considered for the

Purpose of review GBA1 mutations, which result in the lysosomal disorder Gaucher disease, are the most common known genetic risk factor for Parkinson disease and Dementia with Lewy Bodies (DLB). The pathogenesis of this association is not fully understood, but further elucidation of this link could lead to new therapeutic options. Recent findings The characteristic clinical phenotype of GBA1-PD resembles sporadic Parkinson disease, but with an earlier onset and more severe course. Many different GBA1 mutations increase the risk of Parkinson disease, some primarily detected in specific populations. Glucocerebrosidase deficiency appears to be associated with increased α-synuclein aggregation and accumulation, mitochondrial dysfunction because of impaired autophagy, and increased endoplasmic reticulum stress. Summary As our understanding of GBA1-associated Parkinson disease increases, new treatment opportunities emerge. MicroRNA profiles are providing examples of both up-regulated and dow

Purpose of review Corticobasal degeneration (CBD) is a rapidly progressive neurodegenerative tauopathy diagnosed postmortem by pathological examination. The clinical presentation of corticobasal syndrome (CBS) is an apraxic, dystonic, and rigid limb with asymmetrical cortical signs and myoclonus. However, less than half of the patients with CBS receive a CBD diagnosis. As tau-lowering therapies have entered clinical trials, improved antemortem diagnosis of CBD is needed. Here, clinicopathological, neuroimaging, and biofluid data in CBS and/or CBD patients are briefly summarized and some knowledge gaps identified. Recent findings Developments of MRI-based and nuclear medicine imaging modalities have increased pathophysiological insights of CBS and may improve diagnostic accuracy. In particular, several tau-PET ligands have been evaluated in CBS patients. Cerebrospinal fluid and plasma levels of neurofilament light chain can distinguish CBS from Parkinson's disease but not from other

Purpose of review Our understanding of X-Linked Dystonia-Parkinsonism (XDP) has advanced considerably in recent years because of a wealth of new data describing its genetic basis, cellular phenotypes, neuroimaging features, and response to deep brain stimulation (DBS). This review provides a concise summary of these studies. Recent findings XDP is associated with a SINE-VNTR-Alu (SVA)-type retrotransposon insertion within the TAF1 gene. This element includes a hexameric DNA repeat expansion, (CCCTCT)n, the length of which varies among patients and is inversely correlated to age of disease onset. In cell models, the SVA alters TAF1 splicing and reduces levels of full-length transcript. Neuroimaging data have confirmed previous neuropathology studies that XDP involves a progressive striatal atrophy, while further detecting functional alterations in additional brain regions. In patients exhibiting features of both dystonia and parkinsonism, pallidal DBS has resulted in rapid improvement o

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Purpose of review The purpose of this review is to highlight the origin and evolution of the field of neurodevelopmental disabilities and describe the main construct(s) upon which the current classification of neurodevelopmental disorders is based. Recent findings We address the following questions: Are neurodevelopmental disorders independent entities? Why is it desirable to understand the neurobiological substrate for these disorders? What new knowledge have we generated by leveraging advances in neuroscience, genetics, and neuroimaging? And finally, is the current construct, that is based on functional classification, still useful? Summary As our biological understanding of brain-behavior disorders evolves, we ought to re-evaluate the current classification system and expand it into a multidimensional classification that takes into account behavioral profiles and underlying mechanisms. from Current Opinion in Neurology - Current Issue https://ift.tt/2xf9Wg7

Purpose of review To review advances in structural and functional MRI studies regarding the neural underpinnings of social atypicalities in autism spectrum disorder (ASD). Recent findings According to the hypothesis that the social brain network, which includes brain regions, such as the amygdala and superior temporal sulcus, may be atypical in ASD, recent structural MRI studies have identified regional gray matter volume abnormalities in the social brain regions in ASD groups compared with the typically developing groups. Studies evaluating gray matter volume covariance and white matter volume/integrity suggested network-level abnormalities associated with the social brain regions. Recent functional MRI studies assessing resting-state neural activity showed reduced functional connectivity among the social brain regions in individuals with ASD compared with typically developing groups. Similarly, task-based functional MRI studies recently revealed a reduction in regional activity and i

Purpose of review There continues to be more males than females diagnosed with neurodevelopmental disorders, which may provide clues about their cause. This review will focus on the two most common neurodevelopmental disorders – autism spectrum disorder (autism) and attention deficit hyperactivity disorder (ADHD), and explore recent research to understand recent developments in the field. Recent findings Biological mechanisms including genetics, hormones and their interaction with other risk factors, such as stress and lead exposure, point to complex causal pathways for neurodevelopmental disorders. Over recent years, the research focus on sex differences in symptom profiles in autism has continued; however, a meta-analysis of existing studies indicated minimal sex differences in core autism symptoms. In ADHD, changes in the sex ratio from disparity in childhood to parity in adulthood may relate to the onset and trajectory of hyperactivity symptoms in females. Research into medical and

Purpose of review Recent advances in genetic technologies allowed researchers to identify large numbers of candidate risk genes associated with autism spectrum disorder (ASD). Both strongly penetrant rare variants and the accumulation of common variants with much weaker penetrance contribute to the cause of ASD. To identify the highly confident candidate genes, software and resources have been applied, and functional evaluation of the variants has provided further insights for ASD pathophysiology. These studies ultimately identify the molecular and circuit alteration underlying the behavioral abnormalities in ASD. In this review, we introduce the recent genetic and genomic findings and functional approaches for ASD variants providing a deeper understanding of the etiology of ASD. Recent findings Integrated meta-analysis that recruited a larger number of ASD cases has helped to prioritize ASD candidate genes or genetic loci into highly confidence candidate genes for further investigatio

Purpose of review Research on the pathophysiology of syndromic autism spectrum disorder (ASD) has contributed to the uncovering of mechanisms in nonsyndromic ASD. The current review aims to compare recent progress in therapeutics development for ASD with those for fragile X syndrome (FXS), the most frequent monogenic form of ASD. Recent findings Although candidates such as oxytocin, vasopressin, and cannabinoids are being tested as novel therapeutics, it remains difficult to focus on a specific molecular target of drug development for ASD core symptoms. As the pathophysiology of FXS has been well described as having a causal gene, fragile X mental retardation-1, development of therapeutic agents for FXS is focused on specific molecular targets, such as metabotropic glutamate receptor 5 and GABAB receptor. Summary There is a large unmet medical need in ASD, a heterogeneous and clinically defined behavioral syndrome, owing to its high prevalence in the general population, lifelong cognit

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Purpose of review A variety of high-efficacy disease-modifying therapies (DMTs) are available for the treatment of multiple sclerosis (MS). After evaluation and approval by regulatory agencies, DMTs are likely to be administered to patients whose characteristics differ from those enrolled in clinical trials. This may contribute to the emergence of unexpected adverse events observed in the real-world setting. Higher age may be a relevant factor that could change the benefit–risk balance of DMTs, as it may associate with lower efficiency and higher frequency of adverse events. Recent findings The absolute and relative number of patients with MS who reach the age of 55 and higher increases. Growing evidence demonstrates lower efficacy of DMTs in older persons with MS. Specific risks during DMTs for MS, such as the risk of developing progressive multifocal leukoencephalopathy (PML) or the outcome following PML, have been associated with age. It is hypothesized that age-related and therapy-

Purpose of review Research on multiple sclerosis (MS) pathogenesis and therapy is to a large extent driven by results obtained in experimental autoimmune encephalomyelitis (EAE). This approach provided deep insights into the mechanism of brain inflammation and immune mediated tissue injury and, thus, most of our currently established therapies for MS patients have been developed with profound contributions of experimental autoimmune research. Recent data, which are summarized in this review article, however, show important differences between EAE and MS. Recent findings EAE models perfectly reproduce a disease, now called myelin oligodendrocyte glycoprotein (MOG) antibody-associated inflammatory demyelinating disease, which, however, is different from classical MS. In MS, the inflammatory reaction in the brain is dominated by CD8+ T-lymphocyte and CD20+ B cells. Demyelination in MS appears to be triggered by soluble factors, produced by T cells and/or B cells, which are different from

Purpose of review This review provides a brief update of new research findings on the changing epidemiology, disease course, and prognosis of multiple sclerosis (MS). Recent findings Evidence not only continues to support the female predominance in incidence and prevalence of the disease but also supports an increase in incidence of MS in geographic areas that were previously considered to be low incidence for the disease. Summary An increased interest in population-based registries and databases will provide more valid epidemiological measures and observational studies conducted in well-defined study populations. Such studies are crucial for an accurate description of both changing prognosis of MS and differential characteristics of the various MS phenotypes. from Current Opinion in Neurology - Current Issue http://bit.ly/2WfCKzV