Studying human nociceptors: from fundamentals to clinic
AbstractChronic pain affects one in five of the general population and is the third most important cause of disability-adjusted life-years globally. Unfortunately, treatment remains inadequate due to poor efficacy and tolerability. There has been a failure in translating promising preclinical drug targets into clinic use. This reflects challenges across the whole drug development pathway, from preclinical models to trial design. Nociceptors remain an attractive therapeutic target: their sensitization makes an important contribution to many chronic pain states, they are located outside the blood –brain barrier, and th...
Source: Brain - June 21, 2021 Category: Neurology Source Type: research

Annexin A1 restores cerebrovascular integrity concomitant with reduced amyloid- β and tau pathology
AbstractAlzheimer ’s disease, characterized by brain deposits of amyloid-β plaques and neurofibrillary tangles, is also linked to neurovascular dysfunction and blood–brain barrier breakdown, affecting the passage of substances into and out of the brain. We hypothesized that treatment of neurovascular alterations could be beneficial in Alzheimer’s disease. Annexin A1 (ANXA1) is a mediator of glucocorticoid anti-inflammatory action that can suppress microglial activation and reduce blood–brain barrier leakage. We have reported recently that treatment with recombinant human ANXA1 (hrANXA1) reduced...
Source: Brain - June 21, 2021 Category: Neurology Source Type: research

Preventing neurodegenerative disease
As a person ages, the brunt of illness falls increasingly on systems that have limited ability to repair or maintain themselves. Neurons, being post-mitotic, are particularly sensitive in this regard, and the outcome manifests in the increasing prevalence of neurodegenerative disease as the mean age of the population rises. For the individual experiencing a slowing of movement, wasting of a limb, tremor or a failing memory, the onset of symptoms appears to mark the onset of the underlying problem, and people often try to attribute cause based on recent events —‘It all started after the operation’, ‘...
Source: Brain - June 21, 2021 Category: Neurology Source Type: research

Corrigendum to: Molecular and cellular correlates of human nerve regeneration: ADCYAP1/PACAP enhance nerve outgrowth
Georgios Baskozos, Oliver Sandy-Hindmarch, Alex J. Clark, Katherine Windsor, Pall Karlsson, Greg A. Weir, Lucy A. McDermott, Joanna Burchall, Akira Wiberg, Dominic Furniss, David L. H. Bennett and Annina B. Schmid. Molecular and cellular correlates of human nerve regeneration:ADCYAP1/PACAP enhance nerve outgrowth.Brain. 2020;143:2009 –2026. doi:10.1093/brain/awaa163 (Source: Brain)
Source: Brain - June 2, 2021 Category: Neurology Source Type: research

A data-driven approach to post-stroke aphasia classification and lesion-based prediction
AbstractAphasia is an acquired impairment in the production or comprehension of language, typically caused by left hemisphere stroke. The subtyping framework used in clinical aphasiology today is based on the Wernicke-Lichtheim model of aphasia formulated in the late 19th century, which emphasizes the distinction between language production and comprehension. The current study used a data-driven approach that combined modern statistical, machine learning, and neuroimaging tools to examine behavioural deficit profiles and their lesion correlates and predictors in a large cohort of individuals with post-stroke aphasia. First...
Source: Brain - May 27, 2021 Category: Neurology Source Type: research

Pain in Parkinson ’s disease and the role of the subthalamic nucleus
AbstractPain is a frequent and poorly treated symptom of Parkinson ’s disease, mainly due to scarce knowledge of its basic mechanisms. In Parkinson’s disease, deep brain stimulation of the subthalamic nucleus is a successful treatment of motor symptoms, but also might be effective in treating pain. However, it has been unclear which type of pain may benefit and how neurostimulation of the subthalamic nucleus might interfere with pain processing in Parkinson’s disease. We hypothesized that the subthalamic nucleus may be an effective access point for modulation of neural systems subserving pain perception a...
Source: Brain - May 25, 2021 Category: Neurology Source Type: research

Microglial activation and blood –brain barrier leakage: chicken and egg?
This scientific commentary refers to ‘Microglial activation and blood–brain barrier permeability in cerebral small vessel disease’ by Walshet al. (doi:10.1093/brain/awab003). (Source: Brain)
Source: Brain - May 24, 2021 Category: Neurology Source Type: research

Microglial activation and blood –brain barrier permeability in cerebral small vessel disease
AbstractCerebral small vessel disease (SVD) is a major cause of stroke and dementia. The underlying pathogenesis is poorly understood, but both neuroinflammation and increased blood –brain barrier permeability have been hypothesized to play a role, and preclinical studies suggest the two processes may be linked. We used PET magnetic resonance to simultaneously measure microglial activation using the translocator protein radioligand11C-PK11195, and blood –brain barrier permeability using dynamic contrast enhanced MRI. A case control design was used with two disease groups with sporadic SVD (n  = 20...
Source: Brain - May 17, 2021 Category: Neurology Source Type: research

Corrigendum to: De novo stop-loss variants in CLDN11 cause hypomyelinating leukodystrophy
Korbinian M. Riedhammer, Sylvia Stockler, Rafal Ploski, Maren Wenzel, Burkhard Adis-Dutschmann, Uwe Ahting, Bader Alhaddad, Astrid Blaschek, Tobias B. Haack, Robert Kopajtich, Jessica Lee, Victor Murcia Pienkowski, Agnieszka Pollak, Krystyna Szymanska, Maja Tarailo-Graovac, Robin van der Lee, Clara D. van Karnebeek, Thomas Meitinger, Ingeborg Kr ägeloh-Mann, Katharina Vill.De novo stop-loss variants inCLDN11 cause hypomyelinating leukodystrophy.Brain. 2020;144:411 –419. doi:10.1093/brain/awaa410 (Source: Brain)
Source: Brain - May 15, 2021 Category: Neurology Source Type: research

Corrigendum to: A novel RFC1 repeat motif (ACAGG) in two Asia-Pacific CANVAS families
Carolin K. Scriba, Sarah J. Beecroft, Joshua S. Clayton, Andrea Cortese, Roisin Sullivan, Wai Yan Yau, Natalia Dominik, Miriam Rodrigues, Elizabeth Walker, Zoe Dyer, Teddy Y. Wu, Mark R. Davis, David C. Chandler, Ben Weisburd, Henry Houlden, Mary M. Reilly, Nigel G. Laing, Phillipa J. Lamont, Richard H. Roxburgh and Gianina Ravenscroft. A novel RFC1 repeat motif (ACAGG) in two Asia-Pacific CANVAS families.Brain. 2020;143:2904 –2910. doi:10.1093/brain/awaa263 (Source: Brain)
Source: Brain - May 15, 2021 Category: Neurology Source Type: research

The ‘circular inference’ model of schizophrenia gets pulled into the orbit of social cognition
This scientific commentary refers to ‘Taking others into account: combining directly experienced and indirect information in schizophrenia’ by Simonsenet al. (doi:10.1093/brain/awab065). (Source: Brain)
Source: Brain - May 13, 2021 Category: Neurology Source Type: research

Removing the idiopathic from the chronic sensory neuropathies
This scientific commentary refers to ‘RFC1 expansions are a common cause of idiopathic sensory neuropathy ’, by Curròet al. (doi:10.1093/brain/awab072). (Source: Brain)
Source: Brain - May 13, 2021 Category: Neurology Source Type: research

LRRK2 G2019S mutation amplifies protein aggregate propagation
This scientific commentary refers to ‘LRRK2 G2019S kinase activity triggers neurotoxic NSF aggregation’, by Pischeddaet al. (doi:10.1093/brain/awab073). (Source: Brain)
Source: Brain - May 13, 2021 Category: Neurology Source Type: research

ATP1A2- and ATP1A3-associated early profound epileptic encephalopathy and polymicrogyria
AbstractConstitutional heterozygous mutations ofATP1A2 andATP1A3, encoding for two distinct isoforms of the Na+/K+-ATPase (NKA) alpha-subunit, have been associated with familial hemiplegic migraine (ATP1A2), alternating hemiplegia of childhood (ATP1A2/A3), rapid-onset dystonia-parkinsonism, cerebellar ataxia-areflexia-progressive optic atrophy, and relapsing encephalopathy with cerebellar ataxia (allATP1A3). A few reports have described single individuals with heterozygous mutations ofATP1A2/A3 associated with severe childhood epilepsies. Early lethal hydrops fetalis, arthrogryposis, microcephaly, and polymicrogyria have b...
Source: Brain - May 10, 2021 Category: Neurology Source Type: research

Quantitative magnetic resonance imaging towards clinical application in multiple sclerosis
AbstractQuantitative MRI provides biophysical measures of the microstructural integrity of the CNS, which can be compared across CNS regions, patients, and centres. In patients with multiple sclerosis, quantitative MRI techniques such as relaxometry, myelin imaging, magnetization transfer, diffusion MRI, quantitative susceptibility mapping, and perfusion MRI, complement conventional MRI techniques by providing insight into disease mechanisms. These include: (i) presence and extent of diffuse damage in CNS tissue outside lesions (normal-appearing tissue); (ii) heterogeneity of damage and repair in focal lesions; and (iii) s...
Source: Brain - May 10, 2021 Category: Neurology Source Type: research

Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia
We report 25 families containing 34 individuals with neurological disease associated with biallelicHPDL variants. Phenotypes ranged from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spasticity and global developmental delays, sometimes complicated by episodes of neurological and respiratory decompensation. Variants includedbona fide pathogenic truncating changes, although most were missense substitutions. Functionality of variants could not be determined directly as the enzymatic specificity of HPDL is unknown; however, whenHPDL missense substitutions were introduced into 4-hydroxyphenylpyruvate dio...
Source: Brain - May 10, 2021 Category: Neurology Source Type: research

RFC1 expansions are a common cause of idiopathic sensory neuropathy
AbstractAfter extensive evaluation, one-third of patients affected by polyneuropathy remain undiagnosed and are labelled as having chronic idiopathic axonal polyneuropathy, which refers to a sensory or sensory-motor, axonal, slowly progressive neuropathy of unknown origin. Since a sensory neuropathy/neuronopathy is identified in all patients with genetically confirmedRFC1 cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we speculated thatRFC1 expansions could underlie a fraction of idiopathic sensory neuropathies also diagnosed as chronic idiopathic axonal polyneuropathy. We retrospectively identified 225 pati...
Source: Brain - May 9, 2021 Category: Neurology Source Type: research

Dietary conjugated linoleic acid links reduced intestinal inflammation to amelioration of CNS autoimmunity
AbstractA close interaction between gut immune responses and distant organ-specific autoimmunity including the CNS in multiple sclerosis has been established in recent years. This so-called gut –CNS axis can be shaped by dietary factors, either directly or via indirect modulation of the gut microbiome and its metabolites. Here, we report that dietary supplementation with conjugated linoleic acid, a mixture of linoleic acid isomers, ameliorates CNS autoimmunity in a spontaneous mouse mode l of multiple sclerosis, accompanied by an attenuation of intestinal barrier dysfunction and inflammation as well as an increase in...
Source: Brain - May 6, 2021 Category: Neurology Source Type: research

A robust brain signature region approach for episodic memory performance in older adults
This scientific commentary refers to ‘A robust brain signature region approach for episodic memory performance in older adults’ by Fletcheret al. (doi:10.1093/brain/awab007). (Source: Brain)
Source: Brain - May 6, 2021 Category: Neurology Source Type: research

Elucidating autoimmune nodopathies and the CIDP spectrum
This scientific commentary refers to ‘Antibodies to the Caspr1/contactin-1 complex in chronic inflammatory demyelinating polyradiculoneuropathy’, by Pascual-Goñiet al. (doi:10.1093/brain/awab014). (Source: Brain)
Source: Brain - May 6, 2021 Category: Neurology Source Type: research

Reply: Lesion network mapping predicts post-stroke behavioural deficits and improves localization
In their letter to the editor, Cohen and colleagues1 commented on our study2 in which we compared different structural and functional MRI methods to predict behavioural deficits in a large cohort of subacute stroke patients.3 Specifically, we estimated behavioural deficits in different domains (language, vision, motor, attention, and memory) using: (i) lesion location and size; (ii) structural disconnection of white matter pathways estimated in a healthy control atlas (SDC); (iii) functional disconnection of brain networks (FDC) estimated in healthy controls using an approach similar, but not identical to lesion-network ma...
Source: Brain - May 5, 2021 Category: Neurology Source Type: research

Brain microstructural and metabolic alterations detected in vivo at onset of the first demyelinating event
AbstractIn early multiple sclerosis, a clearer understanding of normal-brain tissue microstructural and metabolic abnormalities will provide valuable insights into its pathophysiology. We used multi-parametric quantitative MRI to detect alterations in brain tissues of patients with their first demyelinating episode. We acquired neurite orientation dispersion and density imaging [to investigate morphology of neurites (dendrites and axons)] and23Na MRI (to estimate total sodium concentration, a reflection of underlying changes in metabolic function). In this cross-sectional study, we enrolled 42 patients diagnosed with clini...
Source: Brain - April 27, 2021 Category: Neurology Source Type: research

Lesion network mapping predicts post-stroke behavioural deficits and improves localization
We read with great interest the recent article by Salvalaggio and colleagues comparing the ability of different lesion mapping techniques to predict post-stroke behavioural deficits.1 The authors have been pioneers in this area and previously developed a principal components analysis (PCA)/ridge-regression approach to predict behavioural deficits from lesion location2 and from resting state functional connectivity data obtained in patients after their stroke.3 In their recent paper, Salvalaggioet al. test whether this method can predict behaviour scores based on connectivity with the lesion location generated using normati...
Source: Brain - April 26, 2021 Category: Neurology Source Type: research

Beneficial effects of dipeptidyl peptidase-4 inhibitors in diabetic Parkinson ’s disease
In this study, we hypothesized that treatment with DPP4 inhibitors may have beneficial effects on nigrostriatal dopamine and longitudinal motor performance in diabetic patients with Parkinson ’s disease. We classified 697 drug naive patients withde novo Parkinson ’s disease who had undergone dopamine transporter imaging into three groups according to a prior diagnosis of diabetes and use of DPP4 inhibitors: diabetic patients with Parkinson’s disease being treated with (n  = 54) or without DPP4 inhibitors (n  = 85), and non-diabetic patients with Parkinson ’s disease (n &t...
Source: Brain - April 25, 2021 Category: Neurology Source Type: research

A robust brain signature region approach for episodic memory performance in older adults
We describe a cross-validated signature region model for structural brain components associated with baseline and longitudinal episodic memory across cognitively heterogeneous populations including normal, mild impairment and dementia. We used three non-overlapping cohorts of older participants: from the UC Davis Aging and Diversity cohort (n  = 255; mean age 75.3  ± 7.1 years; 128 cognitively normal, 97 mild cognitive impairment, 30 demented and seven unclassified); from Alzheimer’s Disease Neuroimaging Initiative (ADNI) 1 (n  = 379; mean age 75.1  ±&thi...
Source: Brain - April 25, 2021 Category: Neurology Source Type: research

Emerging principles of brain immunology and immune checkpoint blockade in brain metastases
AbstractBrain metastases are the most common type of brain tumours, harbouring an immune microenvironment that can in principle be targeted via immunotherapy. Elucidating some of the immunological intricacies of brain metastases has opened a therapeutic window to explore the potential of immune checkpoint inhibitors in this globally lethal disease. Multiple lines of evidence suggest that tumour cells hijack the immune regulatory mechanisms in the brain for the benefit of their own survival and progression. Nonetheless, the role of the immune checkpoint in the complex interplays between cancers cells and T cells and in conf...
Source: Brain - April 24, 2021 Category: Neurology Source Type: research

Biallelic loss-of-function variations in PRDX3 cause cerebellar ataxia
AbstractPeroxiredoxin 3 (PRDX3) belongs to a superfamily of peroxidases that function as protective antioxidant enzymes. Among the six isoforms (PRDX1 –PRDX6), PRDX3 is the only protein exclusively localized to the mitochondria, which are the main source of reactive oxygen species. Excessive levels of reactive oxygen species are harmful to cells, inducing mitochondrial dysfunction, DNA damage, lipid and protein oxidation and ultimately apoptosis . Neuronal cell damage induced by oxidative stress has been associated with numerous neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases. L...
Source: Brain - April 23, 2021 Category: Neurology Source Type: research

Spatiotemporal dynamics between interictal epileptiform discharges and ripples during associative memory processing
We describe the spatiotemporal course of cortical high-gamma activity, hippocampal ripple activity and interictal epileptiform discharges during an associative memory task in 15 epilepsy patients undergoing invasive EEG. Successful encoding trials manifested significantly greater high-gamma activity in hippocampus and frontal regions. Successful cued recall trials manifested sustained high-gamma activity in hippocampus compared to failed responses. Hippocampal ripple rates were greater during successful encoding and retrieval trials. Interictal epileptiform discharges during encoding were associated with 15% decreased odds...
Source: Brain - April 23, 2021 Category: Neurology Source Type: research

How understudied populations have contributed to our understanding of Alzheimer ’s disease genetics
AbstractThe majority of genome-wide association studies have been conducted using samples with a broadly European genetic background. As a field, we acknowledge this limitation and the need to increase the diversity of populations studied. A major challenge when designing and conducting such studies is to assimilate large samples sizes so that we attain enough statistical power to detect variants associated with disease, particularly when trying to identify variants with low and rare minor allele frequencies. In this review, we aimed to illustrate the benefits to genetic characterization of Alzheimer ’s disease, in r...
Source: Brain - April 23, 2021 Category: Neurology Source Type: research

A CADM3 variant causes Charcot-Marie-Tooth disease with marked upper limb involvement
AbstractThe CADM family of proteins consists of four neuronal specific adhesion molecules (CADM1, CADM2, CADM3 and CADM4) that mediate the direct contact and interaction between axons and glia. In the peripheral nerve, axon-Schwann cell interaction is essential for the structural organization of myelinated fibres and is primarily mediated by the binding of CADM3, expressed in axons, to CADM4, expressed by myelinating Schwann cells. We have identified —by whole exome sequencing—three unrelated families, including onede novo patient, with axonal Charcot-Marie-Tooth disease (CMT2) sharing the same private variant ...
Source: Brain - April 23, 2021 Category: Neurology Source Type: research

Long-read targeted sequencing uncovers clinicopathological associations for C9orf72-linked diseases
AbstractTo examine the length of a hexanucleotide expansion inC9orf72, which represents the most frequent genetic cause of frontotemporal lobar degeneration and motor neuron disease, we employed a targeted amplification-free long-read sequencing technology: No-Amp sequencing. In our cross-sectional study, we assessed cerebellar tissue from 28 well-characterizedC9orf72 expansion carriers. We obtained 3507 on-target circular consensus sequencing reads, of which 814 bridged theC9orf72 repeat expansion (23%). Importantly, we observed a significant correlation between expansion sizes obtained using No-Amp sequencing and Souther...
Source: Brain - April 23, 2021 Category: Neurology Source Type: research

Corrigendum to: Defective phosphatidylethanolamine biosynthesis leads to a broad ataxia-spasticity spectrum
Rauan Kaiyrzhanov, Saskia Wortmann, Taryn Reid, Mohammadreza Dehghani, Mohammad Yahya Vahidi Mehrjardi, Bader Alhaddad, Matias Wagner, Marcus Deschauer, Isabell Cordts, J. Pedro Fernandez-Murray, Veronika Treffer, Zahra Metanat, Alan Pittman, Henry Houlden, Thomas Meitinger, Christopher Carroll, Christopher R. McMaster, Reza Maroofian. Defective phosphatidylethanolamine biosynthesis leads to a broad ataxia-spasticity spectrum.Brain. 2021;144(3);e30. doi:10.1093/brain/awaa442 (Source: Brain)
Source: Brain - April 21, 2021 Category: Neurology Source Type: research

Cortical involvement determines impairment 30 years after a clinically isolated syndrome
AbstractMany studies report an overlap of MRI and clinical findings between patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), which in part is reflective of inclusion of subjects with variable disease duration and short periods of follow-up. To overcome these limitations, we examined the differences between RRMS and SPMS and the relationship between MRI measures and clinical outcomes 30  years after first presentation with clinically isolated syndrome suggestive of multiple sclerosis. Sixty-three patients were studied 30 years after their initial ...
Source: Brain - April 21, 2021 Category: Neurology Source Type: research

Increased free water in the substantia nigra in idiopathic REM sleep behaviour disorder
In this study, we tested the hypothesis that free water is elevated in the posterior substantia nigra of idiopathic REM sleep behaviour disorder, which is considered a prodromal stage of synucleinopathy. We applied free-water imaging to 32 healthy control subjects, 34 patients with idi opathic REM sleep behaviour disorder and 38 patients with Parkinson’s disease. Eighteen healthy control subjects and 22 patients with idiopathic REM sleep behaviour disorder were followed up and completed longitudinal free-water imaging. Free-water values in the substantia nigra were calculated fo r each individual and compared among g...
Source: Brain - April 21, 2021 Category: Neurology Source Type: research

Disruption of the blood –brain barrier in 22q11.2 deletion syndrome
AbstractNeuroimmune dysregulation is implicated in neuropsychiatric disorders including schizophrenia. As the blood −brain barrier is the immunological interface between the brain and the periphery, we investigated whether this vascular phenotype is intrinsically compromised in the most common genetic risk factor for schizophrenia, the 22q11.2 deletion syndrome (22qDS). Blood−brain barrier like endothelium di fferentiated from human 22qDS+schizophrenia-induced pluripotent stem cells exhibited impaired barrier integrity, a phenotype substantiated in a mouse model of 22qDS. The proinflammatory intercellular adhes...
Source: Brain - April 20, 2021 Category: Neurology Source Type: research

LRRK2 G2019S kinase activity triggers neurotoxic NSF aggregation
AbstractParkinson ’s disease is characterized by the progressive degeneration of dopaminergic neurons within the substantia nigra pars compacta and the presence of protein aggregates in surviving neurons. The LRRK2 G2019S mutation is one of the major determinants of familial Parkinson’s disease cases and leads to late-onset Parkinson’s disease with pleomorphic pathology, including α-synuclein accumulation and deposition of protein inclusions. We demonstrated that LRRK2 phosphorylatesN-ethylmaleimide sensitive factor (NSF). We observed aggregates containing NSF in basal ganglia specimens from patient...
Source: Brain - April 20, 2021 Category: Neurology Source Type: research

Impaired cerebral microcirculation in isolated REM sleep behaviour disorder
AbstractDuring the prodromal period of Parkinson ’s disease and other α-synucleinopathy-related parkinsonisms, neurodegeneration is thought to progressively affect deep brain nuclei, such as the locus coeruleus, caudal raphe nucleus, substantia nigra, and the forebrain nucleus basalis of Meynert. Besides their involvement in the regulation of m ood, sleep, behaviour, and memory functions, these nuclei also innervate parenchymal arterioles and capillaries throughout the cortex, possibly to ensure that oxygen supplies are adjusted according to the needs of neural activity. The aim of this study was to examine whe...
Source: Brain - April 20, 2021 Category: Neurology Source Type: research

Antibodies to the Caspr1/contactin-1 complex in chronic inflammatory demyelinating polyradiculoneuropathy
In conclusion, patients with antibodies to the Caspr1/CNTN1 complex display similar serological and clinical features and constitute a single subgroup within the CIDP syndrome. These antibodies likely target Caspr1 primarily and are detected with Caspr1-only ELISA, but r eactivity is optimal when CNTN1 is added to Caspr1 in cell-based assays and ELISA. (Source: Brain)
Source: Brain - April 20, 2021 Category: Neurology Source Type: research

A serum microRNA sequence reveals fragile X protein pathology in amyotrophic lateral sclerosis
AbstractKnowledge about converging disease mechanisms in the heterogeneous syndrome amyotrophic lateral sclerosis (ALS) is rare, but may lead to therapies effective in most ALS cases. Previously, we identified serum microRNAs downregulated in familial ALS, the majority of sporadic ALS patients, but also in presymptomatic mutation carriers. A 5-nucleotide sequence motif (GDCGG; D  = G, A or U) was strongly enriched in these ALS-related microRNAs. We hypothesized that deregulation of protein(s) binding predominantly to this consensus motif was responsible for the ALS-linked microRNA fingerprint. Using microRNA ...
Source: Brain - April 19, 2021 Category: Neurology Source Type: research

Time for N-of-1 trials in clinical decision-making
Heresy comes in many guises. Sometimes it is spoken softly, wrapped in comforting tones, persuasive despite its wicked subversion. On other occasions, it is delivered with naked provocation, a loud appeal to the rebels. Rarely, it is barely discernible, threaded deftly into an argument which, only on reflection, reveals its shocking, true intent. This one is offered in plain sight: it is time to question the orthodoxy of the way we conduct clinical trials. (Source: Brain)
Source: Brain - April 19, 2021 Category: Neurology Source Type: research

Biallelic variants in LIG3 cause a novel mitochondrial neurogastrointestinal encephalomyopathy
In conclusion, we identified variants in theLIG3 gene that result in a mitochondrial disease characterized by predominant gut dysmotility, encephalopathy, and neuromuscular abnormalities. (Source: Brain)
Source: Brain - April 15, 2021 Category: Neurology Source Type: research

Erratum to: Gamma subunit of complement component 8 is a neuroinflammation inhibitor
Jong-Heon Kim, Ruqayya Afridi, Jin Han, Hyun-Gug Jung, Seung-Chan Kim, Eun Mi Hwang, Hyun Soo Shim, Hoon Ryu, Youngshik Choe, Hyang-Sook Hoe and Kyoungho Suk. Gamma subunit of complement component 8 is a neuroinflammation inhibitor.Brain. 2021;144:528 –552. doi:10.1093/brain/awaa425 (Source: Brain)
Source: Brain - April 14, 2021 Category: Neurology Source Type: research

Alpha-synuclein seeds in olfactory mucosa of patients with isolated REM sleep behaviour disorder
AbstractIsolated REM sleep behaviour disorder (RBD) is an early-stage α-synucleinopathy in most, if not all, affected subjects. Detection of pathological α-synuclein in peripheral tissues of patients with isolated RBD may identify those progressing to Parkinson’s disease, dementia with Lewy bodies or multiple system atrophy, with the ultimate goal of testing preve ntive therapies. Real-time quaking-induced conversion (RT-QuIC) provided evidence of α-synuclein seeding activity in CSF and olfactory mucosa of patients with α-synucleinopathies. The aim of this study was to explore RT-QuIC detectio...
Source: Brain - April 14, 2021 Category: Neurology Source Type: research

De novo purine biosynthesis is a major driver of chemoresistance in glioblastoma
AbstractGlioblastoma is a primary brain cancer with a near 100% recurrence rate. Upon recurrence, the tumour is resistant to all conventional therapies, and because of this, 5-year survival is dismal. One of the major drivers of this high recurrence rate is the ability of glioblastoma cells to adapt to complex changes within the tumour microenvironment. To elucidate this adaptation's molecular mechanisms, specifically during temozolomide chemotherapy, we used chromatin immunoprecipitation followed by sequencing and gene expression analysis. We identified a molecular circuit in which the expression of ciliary protein ADP-ri...
Source: Brain - April 14, 2021 Category: Neurology Source Type: research

Uncovering the prevalence and neural substrates of anhedonia in frontotemporal dementia
AbstractMuch of human behaviour is motivated by the drive to experience pleasure. The capacity to envisage pleasurable outcomes and to engage in goal-directed behaviour to secure these outcomes depends upon the integrity of frontostriatal circuits in the brain. Anhedonia refers to the diminished ability to experience, and to pursue, pleasurable outcomes, and represents a prominent motivational disturbance in neuropsychiatric disorders. Despite increasing evidence of motivational disturbances in frontotemporal dementia (FTD), no study to date has explored the hedonic experience in these syndromes. Here, we present the first...
Source: Brain - April 12, 2021 Category: Neurology Source Type: research

Prevalence and severity of neurovascular compression in hemifacial spasm patients
AbstractHemifacial spasm is typically caused by vascular compression of the proximal intracranial facial nerve. Although the prevalence of neurovascular compression has been investigated in a cohort of patients with classical trigeminal neuralgia, the prevalence and severity of neurovascular compression has not been well characterized in patients with hemifacial spasm. We aimed to investigate whether presence and severity of neurovascular compression are correlated to the symptomatic side in patients with hemifacial spasm. All patients in our study were evaluated by a physician who specializes in the management of cranial ...
Source: Brain - April 11, 2021 Category: Neurology Source Type: research

Neuronal tau species transfer to astrocytes and induce their loss according to tau aggregation state
AbstractDeposits of different abnormal forms of tau in neurons and astrocytes represent key anatomo-pathological features of tauopathies. Although tau protein is highly enriched in neurons and poorly expressed by astrocytes, the origin of astrocytic tau is still elusive. Here, we used innovative gene transfer tools to model tauopathies in adult mouse brains and to investigate the origin of astrocytic tau. We showed in our adeno-associated virus (AAV)-based models and in Thy-Tau22 transgenic mice that astrocytic tau pathology can emerge secondarily to neuronal pathology. By designing anin vivo reporter system, we further de...
Source: Brain - April 11, 2021 Category: Neurology Source Type: research

Functional cognitive disorder: dementia ’s blind spot
We welcome the article by Ball and colleagues on functional cognitive disorder (FCD), since it draws attention to a common and important clinical presentation.1 We agree with the authors that distinguishing cognitive symptoms that have a psychological basis from those that have an organic basis is particularly important in the area of dementia diagnosis. We nevertheless have concerns about some of the key messages in the article. (Source: Brain)
Source: Brain - April 10, 2021 Category: Neurology Source Type: research

Reply: The etymology of ‘neurology’, redux: early use of the term by Jean Riolan the Younger (1610)
It is axiomatic that those who claim priority for dates and details on behalf of specific individuals celebrated in the history of medicine (and other disciplines) give hostages to fortune on the accuracy of who first said ‘what’ and ‘when’. Dr Janssen points out that the Parisian anatomist, Jean Riolan the Younger (1580–1657), used the word ‘neurology’ before Thomas Willis (1621–75).1 We stand corrected. As an aside, unlike Riolan, Willis preferred Greek typography when using the word ‘νευρολογία’, accura...
Source: Brain - April 10, 2021 Category: Neurology Source Type: research

The etymology of ‘neurology’, redux: early use of the term by Jean Riolan the Younger (1610)
(Source: Brain)
Source: Brain - April 10, 2021 Category: Neurology Source Type: research