Concatenating plasma p-tau to Alzheimer ’s disease
This scientific commentary refers to ‘Time course of phosphorylated-tau181 in blood across the Alzheimer’s disease spectrum’, by Moscosoet al. (doi:10.1093/brain/awaa399). (Source: Brain)
Source: Brain - February 12, 2021 Category: Neurology Source Type: research

Neuregulin therapy for multiple sclerosis: an each-way bet?
This scientific commentary refers to ‘Neuregulin-1 beta 1 is implicated in pathogenesis of multiple sclerosis’, by Katariaet al. (doi:10.1093/brain/awaa385). (Source: Brain)
Source: Brain - February 12, 2021 Category: Neurology Source Type: research

An uncertain year: looking back, moving forwards
It is a precarious moment. When people look back at this time they might not view it this way, but as we who are living through it know, we begin the new year on the edge of an extremely uncertain future. Are we on the verge of a way out of the stranglehold that the pandemic had over us in 2020? Will science and the remarkable vaccination programmes that were initiated only months ago provide a decisive solution? Or are we being falsely optimistic about the months ahead? Let us hope not. Let ’s also hope that the spurious claims of the lamentable anti-vaccine movement do not shatter the possibility of a momentous lea...
Source: Brain - February 12, 2021 Category: Neurology Source Type: research

Pathological brain ageing in epilepsy and dementia: two sides of the same coin?
This scientific commentary refers to ‘Atrophy and cognitive profiles in older adults with temporal lobe epilepsy are similar to mild cognitive impairment’, byKaestneret al. (doi:10.1093/brain/awaa397). (Source: Brain)
Source: Brain - February 12, 2021 Category: Neurology Source Type: research

Integrating events in the disintegration of Alzheimer ’s disease
This scientific commentary refers to ‘Untangling the association of amyloid-β and tau with synaptic and axonal loss in Alzheimer’s disease’ by Pereiraet al. (doi:10.1093/brain/awaa395). (Source: Brain)
Source: Brain - February 12, 2021 Category: Neurology Source Type: research

From biomechanics to pathology: predicting axonal injury from patterns of strain after traumatic brain injury
AbstractThe relationship between biomechanical forces and neuropathology is key to understanding traumatic brain injury. White matter tracts are damaged by high shear forces during impact, resulting in axonal injury, a key determinant of long-term clinical outcomes. However, the relationship between biomechanical forces and patterns of white matter injuries, associated with persistent diffusion MRI abnormalities, is poorly understood. This limits the ability to predict the severity of head injuries and the design of appropriate protection. Our previously developed human finite element model of head injury predicted the loc...
Source: Brain - January 17, 2021 Category: Neurology Source Type: research

Neglected cytotoxic T cell invasion of the brain: how specific for Parkinson ’s disease?
This scientific commentary refers to ‘CD8 T cell nigral infiltration precedes synucleinopathy in early stages of Parkinson’s disease’, by Galiano-Landeiraet al. (doi:10.1093/brain/awaa269). (Source: Brain)
Source: Brain - January 13, 2021 Category: Neurology Source Type: research

Situated minds: conceptual and emotional blending in neurodegeneration and beyond
This scientific commentary refers to ‘When affect overlaps with concept: emotion recognition in semantic variant of primary progressive aphasia’, by Bertouxet al. (doi:10.1093/brain/awaa313). (Source: Brain)
Source: Brain - January 13, 2021 Category: Neurology Source Type: research

Unresponsive or just asleep? Do local slow waves in the perilesional cortex have a function?
This scientific commentary refers to ‘Local sleep-like cortical reactivity in the awake brain after focal injury’, by Sarassoet al. (doi:10.1093/brain/awaa338). (Source: Brain)
Source: Brain - January 13, 2021 Category: Neurology Source Type: research

Magnetic resonance spectroscopy reveals mitochondrial dysfunction in amyotrophic lateral sclerosis
This study is the first to assess mitochondrial dysfunction in brain and muscle in individuals living with ALS using31P-magnetic resonance spectroscopy (MRS), the modality of choice to assess energy metabolismin vivo. We recruited 20 patients and 10 healthy age and gender-matched control subjects in this cross-sectional clinico-radiological study.31P-MRS was acquired from cerebral motor regions and from tibialis anterior during rest and exercise. Bioenergetic parameter estimates were derived including: ATP, phosphocreatine, inorganic phosphate, adenosine diphosphate, Gibbs free energy of ATP hydrolysis ( ΔGATP), phos...
Source: Brain - January 13, 2021 Category: Neurology Source Type: research

Editorial
With this issue ofBrain, the current Editor and Associate Editors complete their term of office. In the last 7 years we have scrutinized almost 17  000 submissions, from which we have selected for publication 1580 Original Articles, Reports and Clinical Trials, 84 Editorials, 80 Reviews, 34 Updates, 332 Scientific Commentaries, and 121 other items such as Book Reviews and Grey Matters, filling over 25 000 pages spread across 84 issues. Thi s is not counting material that has appeared online but not in the print journal, mainly Letters to the Editor, but also Corrigenda, Evoked Responses, and Retractions (than...
Source: Brain - January 13, 2021 Category: Neurology Source Type: research

Increased O-GlcNAcylation prevents degeneration of dopamine neurons
This scientific commentary refers to ‘O-GlcNAcylation regulates dopamine neuron function, survival and degeneration in Parkinson disease ’, by Lee et al. (doi:10.1093/brain/awaa320). (Source: Brain)
Source: Brain - January 13, 2021 Category: Neurology Source Type: research

Serum neurofilament light chain uncovers neurodegeneration early in the course of Alzheimer ’s disease
This scientific commentary refers to ‘Stage-specific links between plasma neurofilament light and imaging biomarkers of Alzheimer’s disease’, by Benedetet al. (doi:10.1093/brain/awaa342). (Source: Brain)
Source: Brain - January 9, 2021 Category: Neurology Source Type: research

Natural history of Charcot-Marie-Tooth disease type 2A: a large international multicentre study
AbstractMitofusin-2 (MFN2) is one of two ubiquitously expressed homologous proteins in eukaryote cells, playing a critical role in mitochondrial fusion. Mutations inMFN2 (most commonly autosomal dominant) cause Charcot-Marie-Tooth disease type 2A (CMT2A), the commonest axonal form of CMT, with significant allelic heterogeneity. Previous, moderately-sized, cross sectional genotype-phenotype studies of CMT2A have described the phenotypic spectrum of the disease, but longitudinal natural history studies are lacking. In this large multicentre prospective cohort study of 196 patients with dominant and autosomal recessive CMT2A,...
Source: Brain - January 8, 2021 Category: Neurology Source Type: research

Dopaminergic imaging and clinical predictors for phenoconversion of REM sleep behaviour disorder
AbstractThis is an international multicentre study aimed at evaluating the combined value of dopaminergic neuroimaging and clinical features in predicting future phenoconversion of idiopathic REM sleep behaviour (iRBD) subjects to overt synucleinopathy. Nine centres sent123I-FP-CIT-SPECT data of 344 iRBD patients and 256 controls for centralized analysis.123I-FP-CIT-SPECT images were semiquantified using DaTQUANTTM, obtaining putamen and caudate specific to non-displaceable binding ratios (SBRs). The following clinical variables were also analysed: (i) Movement Disorder Society-sponsored revision of the Unified Parkinson &...
Source: Brain - December 29, 2020 Category: Neurology Source Type: research

Abnormal dorsal attention network activation in memory impairment after traumatic brain injury
AbstractMemory impairment is a common, disabling effect of traumatic brain injury. In healthy individuals, successful memory encoding is associated with activation of the dorsal attention network as well as suppression of the default mode network. Here, in traumatic brain injury patients we examined whether: (i) impairments in memory encoding are associated with abnormal brain activation in these networks; (ii) whether changes in this brain activity predict subsequent memory retrieval; and (iii) whether abnormal white matter integrity underpinning functional networks is associated with impaired subsequent memory. Thirty-fi...
Source: Brain - December 26, 2020 Category: Neurology Source Type: research

Vestibular agnosia in traumatic brain injury and its link to imbalance
In conclusion, vestibular agnosia mediates imbalance in traumatic brain injury both directly via white matter tract damage in the right temporal lobe, and indirectly via reduced clinical recognition of common, treatable vestibular diagnoses. (Source: Brain)
Source: Brain - December 26, 2020 Category: Neurology Source Type: research

How do the blind ‘see’? The role of spontaneous brain activity in self-generated perception
AbstractSpontaneous activity of the human brain has been well documented, but little is known about the functional role of this ubiquitous neural phenomenon. It has previously been hypothesized that spontaneous brain activity underlies unprompted (internally generated) behaviour. We tested whether spontaneous brain activity might underlie internally-generated vision by studying the cortical visual system of five blind/visually-impaired individuals who experience vivid visual hallucinations (Charles Bonnet syndrome). Neural populations in the visual system of these individuals are deprived of external input, which may lead ...
Source: Brain - December 26, 2020 Category: Neurology Source Type: research

Reply: Concentric demyelination pattern in COVID-19-associated acute haemorrhagic leukoencephalitis: a lurking catastrophe?
We are grateful toKarapanayiotides and colleagues (2020) for their description of a 57-year-old patient with acute haemorrhagic leukoencephalitis (AHLE) and concentric demyelination suggestive of Bal ó’s disease, and for adding insights into the neurological manifestations of COVID-19. The authors are correct to point out that the mechanisms underpinning the features in all of our collective patients remain to be determined, and the role of direct infection, hypoxia, immune-mediated injury an d metabolic processes all warrant further exploration. The authors are also correct in describing the difficulty in app...
Source: Brain - December 16, 2020 Category: Neurology Source Type: research

Inhibitory control dysfunction in parkinsonian impulse control disorders
AbstractImpulse control disorders (ICDs) in Parkinson ’s disease have been associated with dysfunctions in the control of value- or reward-based responding (choice impulsivity) and abnormalities in mesocorticolimbic circuits. The hypothesis that dysfunctions in the control of response inhibition (action impulsivity) also play a role in Parkinson’s disease ICDs has recently been raised, but the underlying neural mechanisms have not been probed directly. We used high-resolution EEG recordings from 41 patients with Parkinson’s disease with and without ICDs to track the spectral and dynamical signatures of di...
Source: Brain - December 15, 2020 Category: Neurology Source Type: research

Tissue-resident CD8+ memory T cells in multiple sclerosis
We read with interest the article byFransenet al. (2020) inBrain. The authors studied the role of CD8+ T cells in a large cohort of chronic multiple sclerosis autopsy cases from the Netherlands Brain Bank. In all white matter samples, CD8+ T cells were conspicuous in the perivascular space (PVS; Virchow-Robin space). At the level of postcapillary venules where lymphocyte extravasation takes place, this specialized compartment is bordered by the endothelial basement membrane on the vascular side, and the glia limitans on the brain parenchymal side (Engelhardtet al., 2017). A large proportion of the CD8+ cells displayed the ...
Source: Brain - December 13, 2020 Category: Neurology Source Type: research

Reply: Tissue-resident CD8+ memory T cells in multiple sclerosis
We thankHohlfieldet al. (2020) for their appreciation and discussion of our work. Our data provide an extension of the data earlier reported byMachado-Santoset al. (2018). We showed that white matter perivascular CD8+ T cells of multiple sclerosis donors co-expressed CD69 with variable levels of CD103 and CD49a, PD-1, and CXCR6 (Fransenet al., 2020), characterizing them as tissue-resident memory T (TRM) cells (Kumaret al., 2017). (Source: Brain)
Source: Brain - December 13, 2020 Category: Neurology Source Type: research

Neuregulin-1 beta 1 is implicated in pathogenesis of multiple sclerosis
AbstractMultiple sclerosis is characterized by immune mediated neurodegeneration that results in progressive, life-long neurological and cognitive impairments. Yet, the endogenous mechanisms underlying multiple sclerosis pathophysiology are not fully understood. Here, we provide compelling evidence that associates dysregulation of neuregulin-1 beta 1 (Nrg-1 β1) with multiple sclerosis pathogenesis and progression. In the experimental autoimmune encephalomyelitis model of multiple sclerosis, we demonstrate that Nrg-1β1 levels are abated within spinal cord lesions and peripherally in the plasma and spleen during pr...
Source: Brain - December 13, 2020 Category: Neurology Source Type: research

Platelet-derived growth factor beta is a potent inflammatory driver in paediatric high-grade glioma
AbstractPaediatric high-grade gliomas (HGGs) account for the most brain tumour-related deaths in children and have a median survival of 12 –15 months. One promising avenue of research is the development of novel therapies targeting the properties of non-neoplastic cell-types within the tumour such as tumour associated macrophages (TAMs). TAMs are immunosuppressive and promote tumour malignancy in adult HGG; however, in paediatric med ulloblastoma, TAMs exhibit anti-tumour properties. Much is known about TAMs in adult HGG, yet little is known about them in the paediatric setting. This raises the question of whether pa...
Source: Brain - December 10, 2020 Category: Neurology Source Type: research

Bird watching on the asphalt
Attempting to make a diagnosis from a collection of baffling symptoms is comparable to the challenge of identifying an unusual bird that refuses to stay still. Andrew Lees describes how bird watching and a love of natural history helped turn him not only into a noticer, but ultimately into a neurologist. (Source: Brain)
Source: Brain - December 10, 2020 Category: Neurology Source Type: research

Trigeminal neurovascular contact in SUNCT and SUNA: a cross-sectional magnetic resonance study
AbstractEmerging data-points towards a possible aetiological and therapeutic relevance of trigeminal neurovascular contact in short lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and perhaps in short lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA). We aimed to assess the prevalence and significance of trigeminal neurovascular contact in a large cohort of consecutive SUNCT and SUNA patients and evaluate the radiological differences between them. The standard imaging protocol included high spatial and nerve-cistern contrast resolution i...
Source: Brain - December 10, 2020 Category: Neurology Source Type: research

Developmental and epileptic encephalopathies: what we do and do not know
AbstractDevelopmental encephalopathies, including intellectual disability and autistic spectrum disorder, are frequently associated with infant epilepsy. Epileptic encephalopathy is used to describe an assumed causal relationship between epilepsy and developmental delay. Developmental encephalopathies pathogenesis more independent from epilepsy is supported by the identification of several gene variants associated with both developmental encephalopathies and epilepsy, the possibility for gene-associated developmental encephalopathies without epilepsy, and the continued development of developmental encephalopathies even whe...
Source: Brain - December 5, 2020 Category: Neurology Source Type: research

Untangling the association of amyloid- β and tau with synaptic and axonal loss in Alzheimer’s disease
AbstractIt is currently unclear how amyloid- β and tau deposition are linked to changes in synaptic function and axonal structure over the course of Alzheimer’s disease. Here, we assessed these relationships by measuring presynaptic (synaptosomal-associated protein 25, SNAP25; growth-associated protein 43, GAP43), postsynaptic (neurogranin, NRGN) and axonal (neurofilament light chain) markers in the CSF of individuals with varying levels of amyloid-β and tau pathology based on18F-flutemetamol PET and18F-flortaucipir PET. In addition, we explored the relationships between synaptic and axonal markers with cog...
Source: Brain - December 5, 2020 Category: Neurology Source Type: research

Atrophy and cognitive profiles in older adults with temporal lobe epilepsy are similar to mild cognitive impairment
AbstractEpilepsy incidence and prevalence peaks in older adults yet systematic studies of brain ageing and cognition in older adults with epilepsy remain limited. Here, we characterize patterns of cortical atrophy and cognitive impairment in 73 older adults with temporal lobe epilepsy (>55 years) and compare these patterns to those observed in 70 healthy controls and 79 patients with amnestic mild cognitive impairment, the prodromal stage of Alzheimer ’s disease. Patients with temporal lobe epilepsy were recruited from four tertiary epilepsy surgical centres; amnestic mild cognitive impairment and control subjects...
Source: Brain - December 5, 2020 Category: Neurology Source Type: research

Genetic, cellular, and connectomic characterization of the brain regions commonly plagued by glioma
AbstractFor decades, it has been known that gliomas follow a non-random spatial distribution, appearing more often in some brain regions (e.g. the insula) compared to others (e.g. the occipital lobe). A better understanding of the localization patterns of gliomas could provide clues to the origins of these types of tumours, and consequently inform treatment targets. Following hypotheses derived from prior research into neuropsychiatric disease and cancer, gliomas may be expected to localize to brain regions characterized by functional hubness, stem-like cells, and transcription of genetic drivers of gliomagenesis. We combi...
Source: Brain - December 4, 2020 Category: Neurology Source Type: research

Tremor in Parkinson's disease inverts the effect of dopamine on reinforcement
This scientific commentary refers to ‘Effects of dopamine on reinforcement learning in Parkinson’s disease depend on motor phenotype’ by van Nulandet al. (doi:10.1093/brain/awaa335). (Source: Brain)
Source: Brain - December 4, 2020 Category: Neurology Source Type: research

Mitochondria and Parkinson ’s disease: a complex (III) liaison
This scientific commentary refers to ‘MitochondrialUQCRC1 mutations cause autosomal dominant parkinsonism with polyneuropathy ’, by Linet al. (doi:10.1093/brain/awaa279). (Source: Brain)
Source: Brain - December 4, 2020 Category: Neurology Source Type: research

Severe COVID-19-related encephalitis can respond to immunotherapy
This article provides major categories of COVID-19-related neurological syndromes, including patients with encephalitis, and reports corticosteroids and intravenous immunoglobulin response in some patients. Indeed, various COVID-19-related neurological syndromes have been reported since December 2019 (Filatovet al., 2020;Helmset al., 2020;Khooet al., 2020;Maoet al., 2020;Moriguchiet al., 2020;Oxleyet al., 2020;Poyiadjiet al., 2020). However, encephalitis has seldom been reported and the potential benefit of immunotherapy remains unclear (one of two patients improved inPatersonet al., 2020). Herein, we report a case series ...
Source: Brain - December 2, 2020 Category: Neurology Source Type: research

The microglial component of amyotrophic lateral sclerosis
AbstractMicroglia are the primary immune cells of the CNS, carrying out key homeostatic roles and undergoing context-dependent and temporally regulated changes in response to injury and neurodegenerative diseases. Microglia have been implicated in playing a role in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by extensive motor neuron loss leading to paralysis and premature death. However, as the pathomechansims of ALS are increasingly recognized to involve a multitude of different cell types, it has been difficult to delineate the specific contribution of microglia to disease. Here, we re...
Source: Brain - December 2, 2020 Category: Neurology Source Type: research

Erratum to: Dystonia genes functionally converge in specific neurons and share neurobiology with psychiatric disorders
Niccol ò E. Mencacci, Regina Reynolds, Sonia Garcia Ruiz, Jana Vandrovcova, Paola Forabosco, Alvaro Sánchez-Ferrer, Viola Volpato, UK Brain Expression Consortium, International Parkinson’s Disease Genomics Consortium, Michael E. Weale, Kailash P. Bhatia, Caleb Webber, John Hardy, Juan A. Botía, Mina R yten. Dystonia genes functionally converge in specific neurons and share neurobiology with psychiatric disorders. Brain 2020; 143: 2771–2787. doi:10.1093/brain/awaa217. (Source: Brain)
Source: Brain - December 1, 2020 Category: Neurology Source Type: research

A novel de novo SPTAN1 nonsense variant causes hereditary motor neuropathy in a Chinese family
It was with great interest that we read the article published byBeijeret al. (2019) about autosomal dominant distal hereditary motor neuropathy (dHMN) caused by pathogenic variants in the αII-spectrin gene (SPTAN1; OMIM 182810). Using whole exome sequencing (WES) or whole genome sequencing (WGS), the authors identified three nonsense heterozygous mutations, c.415C>T (p.Arg139*), c.4615C>T (p.Gln1539*) and c.6460C>T (p.Gln2154*), in three dHMN families. Although the penetrance and severity of the disease were highly variable, most affected patients had juvenile onset of axonal motor neuropathy characterized b...
Source: Brain - December 1, 2020 Category: Neurology Source Type: research

Acute and non-resolving inflammation associate with oxidative injury after human spinal cord injury
AbstractTraumatic spinal cord injury is a devastating insult followed by progressive cord atrophy and neurodegeneration. Dysregulated or non-resolving inflammatory processes can disturb neuronal homeostasis and drive neurodegeneration. Here, we provide an in-depth characterization of innate and adaptive inflammatory responses as well as oxidative tissue injury in human traumatic spinal cord injury lesions compared to non-traumatic control cords. In the lesion core, microglia were rapidly lost while intermediate (co-expressing pro- as well as anti-inflammatory molecules) blood-borne macrophages dominated. In contrast, in th...
Source: Brain - December 1, 2020 Category: Neurology Source Type: research

The accumulation rate of tau aggregates is higher in females and younger amyloid-positive subjects
AbstractThe development of tau-PET allows paired helical filament tau pathology to be visualizedin vivo. Increased knowledge about conditions affecting the rate of tau accumulation could guide the development of therapies halting the progression of Alzheimer ’s disease. However, the factors modifying the rate of tau accumulation over time in Alzheimer’s disease are still largely unknown. Large-scale longitudinal cohort studies, adjusting for baseline tau load, are needed to establish such risk factors. In the present longitudinal study, 419 particip ants from four cohorts in the USA (Avid 05e,n  =&thinsp...
Source: Brain - December 1, 2020 Category: Neurology Source Type: research

Plasma p-tau217: from ‘new kid’ to most promising candidate for Alzheimer’s disease blood test
This scientific commentary refers to ‘Longitudinal plasma p-tau217 is increased in early stages of Alzheimer’s disease’, by Mattsson-Carlgrenet al. (doi:10.1093/brain/awaa286). (Source: Brain)
Source: Brain - December 1, 2020 Category: Neurology Source Type: research

Is bad brain worse than no brain? Salvaging the cerebral cortex in epilepsy
This scientific commentary refers to ‘Resective surgery prevents progressive cortical thinning in temporal lobe epilepsy’, by Galovicet al. (doi:10.1093/brain/awaa284). (Source: Brain)
Source: Brain - December 1, 2020 Category: Neurology Source Type: research

Non-invasive quantification of inflammation, axonal and myelin injury in multiple sclerosis
AbstractThe aim of this study was to determine the feasibility of diffusion basis spectrum imaging in multiple sclerosis at 7 T and to investigate the pathological substrates of tissue damage in lesions and normal-appearing white matter. To this end, 43 patients with multiple sclerosis (24 relapsing-remitting, 19 progressive), and 21 healthy control subjects were enrolled. White matter lesions were classified in T1-isointense, T1-hypointense and black holes. Mean values of diffusion basis spectrum imaging metrics (fibres, restricted and non-restricted fractions, axial and radial diffusivities and fractional anisotropy) wer...
Source: Brain - November 30, 2020 Category: Neurology Source Type: research

Subthalamic stimulation impairs stopping of ongoing movements
AbstractThe subthalamic nucleus is part of a global stopping network that also includes the presupplementary motor area and inferior frontal gyrus of the right hemisphere. In Parkinson ’s disease, subthalamic deep brain stimulation improves movement initiation and velocity, but its effect on stopping of ongoing movement is unknown. Here, we examine the relation between movement stopping and connectivity of stimulation volumes to the stopping network. Stop and go times were colle cted in 17 patients with Parkinson’s disease on and off subthalamic stimulation during visually cued initiation and termination of con...
Source: Brain - November 30, 2020 Category: Neurology Source Type: research

Retinal asymmetry in multiple sclerosis
AbstractThe diagnosis of multiple sclerosis is based on a combination of clinical and paraclinical tests. The potential contribution of retinal optical coherence tomography (OCT) has been recognized. We tested the feasibility of OCT measures of retinal asymmetry as a diagnostic test for multiple sclerosis at the community level. In this community-based study of 72  120 subjects, we examined the diagnostic potential of the inter-eye difference of inner retinal OCT data for multiple sclerosis using the UK Biobank data collected at 22 sites between 2007 and 2010. OCT reporting and quality control guidelines were follow...
Source: Brain - November 30, 2020 Category: Neurology Source Type: research

Time course of phosphorylated-tau181 in blood across the Alzheimer ’s disease spectrum
We examined longitudinal data from a large prospective cohort of elderly individuals enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (n  = 1067) covering a wide clinical spectrum from normal cognition to dementia, and with measures of plasma p-tau181 and an18F-florbetapir amyloid- β PET scan at baseline. A subset of participants (n  = 864) also had measures of amyloid- β1 –42 and p-tau181 levels in CSF, and another subset (n  = 298) had undergone an18F-flortaucipir tau PET scan 6 years later. We performed brain-wide analyses to investigate t...
Source: Brain - November 30, 2020 Category: Neurology Source Type: research

Detecting axonal injury in individual patients after traumatic brain injury
AbstractPoor outcomes after traumatic brain injury (TBI) are common yet remain difficult to predict. Diffuse axonal injury is important for outcomes, but its assessment remains limited in the clinical setting. Currently, axonal injury is diagnosed based on clinical presentation, visible damage to the white matter or via surrogate markers of axonal injury such as microbleeds. These do not accurately quantify axonal injury leading to misdiagnosis in a proportion of patients. Diffusion tensor imaging provides a quantitative measure of axonal injuryin vivo, with fractional anisotropy often used as a proxy for white matter dama...
Source: Brain - November 30, 2020 Category: Neurology Source Type: research

FUS is lost from nuclei and gained in neurites of motor neurons in a human stem cell model of VCP-related ALS
(Source: Brain)
Source: Brain - November 30, 2020 Category: Neurology Source Type: research

BACE inhibition causes rapid, regional, and non-progressive volume reduction in Alzheimer ’s disease brain
AbstractIn the phase 3 EPOCH trial (Clinicaltrials.gov; NCT01739348), treatment with the BACE inhibitor verubecestat failed to improve cognition in patients with mild-to-moderate Alzheimer ’s disease, but was associated with reduced hippocampal volume after 78 weeks as assessed by MRI. The aims of the present exploratory analyses were to: (i) characterize the effect of verubecestat on brain volume by evaluating the time course of volumetric MRI changes for a variety of brain regions ; and (ii) understand the mechanism through which verubecestat might cause hippocampal (and other brain region) volume loss by assessing...
Source: Brain - November 30, 2020 Category: Neurology Source Type: research

Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis
In this study (trial registration: NCT02166021), we aimed to evaluate the optimal way of administration, the safety and the clinical efficacy of mesenchymal stem cell (MSC) transplantation in patients with active and progressive multiple sclerosis. Forty-eight patients (28 males and 20 females) with progressive multiple sclerosis (Expanded Disability Status Scale: 3.0 –6.5, mean : 5.6 ± 0.8, mean age: 47.5 ± 12.3) and evidence of either clinical worsening or activity during the previous year, were enrolled (between 2015 and 2018). Patients were randomized into three groups an...
Source: Brain - November 30, 2020 Category: Neurology Source Type: research

Brain cancer induces systemic immunosuppression through release of non-steroid soluble mediators
AbstractImmunosuppression of unknown aetiology is a hallmark feature of glioblastoma and is characterized by decreased CD4 T-cell counts and downregulation of major histocompatibility complex class II expression on peripheral blood monocytes in patients. This immunosuppression is a critical barrier to the successful development of immunotherapies for glioblastoma. We recapitulated the immunosuppression observed in glioblastoma patients in the C57BL/6 mouse and investigated the aetiology of low CD4 T-cell counts. We determined that thymic involution was a hallmark feature of immunosuppression in three distinct models of bra...
Source: Brain - November 30, 2020 Category: Neurology Source Type: research

Editorial
This is the penultimate issue ofBrain edited by the current team, before the journal is handed over to Professor Masud Husain and his colleagues. I shall leave the thanks and farewells to the December issue, and instead take this opportunity to reflect on the mixture of duties and responsibilities that come with the position of Editor-in-Chief of an established biomedical journal. Following in the footsteps of giants such as John Hughlings Jackson, David Ferrier, Henry Head and Gordon Holmes also brings some degree of anxiety to the job: the risks of crashing the vehicle outweigh the likely benefits of making radical chang...
Source: Brain - November 30, 2020 Category: Neurology Source Type: research