Cell-binding IgM in CSF is distinctive of multiple sclerosis and targets the iron transporter SCARA5
AbstractIntrathecal IgM production in multiple sclerosis is associated with a worse disease course. To investigate pathogenic relevance of autoreactive IgM in multiple sclerosis, CSF from two independent cohorts, including multiple sclerosis patients and controls, were screened for antibody binding to induced pluripotent stem cell-derived neurons and astrocytes, and a panel of CNS-related cell lines. IgM binding to a primitive neuro-ectodermal tumour cell line discriminated 10% of multiple sclerosis donors from controls. Transcriptomes of single IgM producing CSF B cells from patients with cell-binding IgM were sequenced a...
Source: Brain - December 20, 2023 Category: Neurology Source Type: research
Amidst an amygdala renaissance in Alzheimer ’s disease
AbstractThe amygdala was highlighted as an early site for neurofibrillary tau tangle pathology in Alzheimer ’s disease in the seminal 1991 article by Braak and Braak. This knowledge has, however, only received traction recently with advances in imaging and image analysis techniques. Here, we provide a cross-disciplinary overview of pathology and neuroimaging studies on the amygdala.These studies provide strong support for an early role of the amygdala in Alzheimer’s disease and the utility of imaging biomarkers of the amygdala in detecting early changes and predicting decline in cognitive functions and neuropsychiatric...
Source: Brain - December 18, 2023 Category: Neurology Source Type: research
Epilepsy in childhood and school performance: a nation-wide cohort study
In conclusion, childhood epilepsy was as sociated with impaired academic performance throughout schooling, which suggest that there is a widespread need for educational support of children with epilepsy, even when the child has no other comorbidities and when the epilepsy appears well-managed. (Source: Brain)
Source: Brain - December 16, 2023 Category: Neurology Source Type: research
Anti-seizure gene therapy for focal cortical dysplasia
AbstractFocal cortical dysplasias are a common subtype of malformation of cortical development, which frequently presents with a spectrum of cognitive and behavioural abnormalities as well as pharmacoresistant epilepsy. Focal cortical dysplasia type II is typically caused by somatic mutations resulting in mammalian target of rapamycin (mTOR) hyperactivity, and is the commonest pathology found in children undergoing epilepsy surgery. However, surgical resection does not always result in seizure freedom, and is often precluded by proximity to eloquent brain regions. Gene therapy is a promising potential alternative treatment...
Source: Brain - December 15, 2023 Category: Neurology Source Type: research
Dengue virus infection and neurological manifestations: an update
AbstractDengue virus is a flavivirus transmitted by the mosquitoes,Aedes aegypti andAedes albopictus. Dengue infection by all four serotypes (DEN 1 to 4) is endemic globally in regions with tropical and subtropical climates, with an estimated 100 –400 million infections annually. Among those hospitalized, the mortality is about 1%. Neurological involvement has been reported to be about 5%. The spectrum of neurological manifestations spans both the peripheral and central nervous systems. These manifestations could possibly be categorized in to those directly related to dengue infection, i.e. acute and chronic encephalitis...
Source: Brain - December 11, 2023 Category: Neurology Source Type: research
Physick to Physiology
(Source: Brain)
Source: Brain - December 11, 2023 Category: Neurology Source Type: research
Extracellular vesicle proteome unveils cathepsin B connection to Alzheimer ’s disease pathogenesis
AbstractExtracellular vesicles (EVs) are membrane vesicles that are released extracellularly and considered to be implicated in the pathogenesis of neurodegenerative diseases including Alzheimer ’s disease. Here, CSF EVs of 16 ATN-classified cases were subjected to quantitative proteome analysis. In these CSF EVs, levels of 11 proteins were significantly altered during the ATN stage transitions (P< 0.05 and fold-change> 2.0). These proteins were thought to be associated with Alzheimer ’s disease pathogenesis and represent candidate biomarkers for pathogenic stage classification. Enzyme-linked immunosorbent assay ...
Source: Brain - December 10, 2023 Category: Neurology Source Type: research
Integrating direct electrical brain stimulation with the human connectome
AbstractNeurological and neurodevelopmental conditions are a major public health concern for which new therapies are urgently needed. The development of effective therapies relies on the precise mapping of the neural substrates causally involved in behaviour generation. Direct electrical stimulation (DES) performed during cognitive and neurological monitoring in awake surgery is currently considered the gold standard for the causal mapping of brain functions. However, DES is limited by the focal nature of the stimulation sites, hampering a real holistic exploration of human brain functions at the network level.We used 4137...
Source: Brain - December 4, 2023 Category: Neurology Source Type: research
Expression profiling of cerebrospinal fluid identifies dysregulated antiviral mechanisms in multiple sclerosis
AbstractDespite the overwhelming evidence that multiple sclerosis is an autoimmune disease, relatively little is known about the precise nature of the immune dysregulation underlying the development of the disease.Reasoning that the CSF from patients might be enriched for cells relevant in pathogenesis, we have completed a high-resolution single-cell analysis of 96 732 CSF cells collected from 33 patients with multiple sclerosis (n = 48 675) and 48 patients with other neurological diseases (n = 48 057).Completing comprehensive cell type annotation, we identified a rare population of CD8+ T cells, characterized by the upreg...
Source: Brain - December 1, 2023 Category: Neurology Source Type: research
Nigrostriatal tau pathology in parkinsonism and Parkinson ’s disease
AbstractWhile Parkinson ’s disease remains clinically defined by cardinal motor symptoms resulting from nigrostriatal degeneration, it is now appreciated that the disease commonly consists of multiple pathologies, but it is unclear where these co-pathologies occur early in disease and whether they are responsible for the nigrostriatal degeneration.For the past number of years, we have been studying a well-characterized cohort of subjects with motor impairment that we have termed mild motor deficits. Motor deficits were determined on a modified and validated Unified Parkinson’s Disease Rating Scale III but were in suffi...
Source: Brain - November 25, 2023 Category: Neurology Source Type: research
Neuromelanin? MRI of catecholaminergic neurons
With great interest I read the review article by Trujilloet al.1 As given in the abstract, our recent observation2,3 suggests ‘that the main source of the NM-MRI contrast is not the presence of neuromelanin [NM] but the high water content in the dopaminergic [DA] and noradrenergic [NA] neurons’. In fact, our observation2,3 of longer T1 and higher proton density in the locus coeruleus (LC) than in other brain regions is in agreement with the observation4,5 of the authors. They showed that the substantia nigra (SN) and LC have lower macromolecular-to-free-water pool size ratio compared to other structures. Further, hyper...
Source: Brain - November 18, 2023 Category: Neurology Source Type: research
Reply: Neuromelanin? MRI of catecholaminergic neurons
We express our gratitude to Dr Watanabe1 for the editorial comment regarding our review article2 and the thought-provoking discussion concerning the origins of neuromelanin (NM)-MRI contrast. Considering the increasing clinical interest in NM-MRI, gaining a profound understanding of the contrast mechanisms responsible for this signal is crucial, as it directly impacts the accurate interpretation of NM-MRI findings. The author has summarized the various mechanisms associated with this contrast, underscoring the importance of the high-water content within the dopaminergic neurons of the substantia nigra (SN) and the noradren...
Source: Brain - November 18, 2023 Category: Neurology Source Type: research
Neural stem cell therapies for spinal cord injury repair: an update on recent preclinical and clinical advances
AbstractTraumatic spinal cord injury (SCI) is a leading cause of lifelong disabilities. Permanent sensory, motor and autonomic impairments after SCI are substantially attributed to degeneration of spinal cord neurons and axons, and disintegration of neural network. To date, minimal regenerative treatments are available for SCI with an unmet need for new therapies to reconstruct the damaged spinal cord neuron-glia network and restore connectivity with the supraspinal pathways.Multipotent neural precursor cells (NPCs) have a unique capacity to generate neurons, oligodendrocytes and astrocytes. Due to this capacity, NPCs have...
Source: Brain - November 17, 2023 Category: Neurology Source Type: research
The prefrontal cortex: from monkey to man
AbstractThe prefrontal cortex is so important to human beings that, if deprived of it, our behaviour is reduced to action-reactions and automatisms, with no ability to make deliberate decisions. Why does the prefrontal cortex hold such importance in humans? In answer, this review draws on the proximity between humans and other primates, which enables us, through comparative anatomical-functional analysis, to understand the cognitive functions we have in common and specify those that distinguish humans from their closest cousins.First, a focus on the lateral region of the prefrontal cortex illustrates the existence of a con...
Source: Brain - November 16, 2023 Category: Neurology Source Type: research
Correction to: Normal and pathogenic variation of RFC1 repeat expansions: implications for clinical diagnosis
Natalia Dominik, Stefania Magri, Riccardo Curr ò, Elena Abati, Stefano Facchini, Marinella Corbetta, Hannah Macpherson, Daniela Di Bella, Elisa Sarto, Igor Stevanovski, Sanjog R. Chintalaphani, Fulya Akcimen, Arianna Manini, Elisa Vegezzi, Ilaria Quartesan, Kylie-Ann Montgomery, Valentina Pirota, Emmanuele Crespan, Cecilia Perini, Glenda Paola Grupelli, Pedro J. Tomaselli, Wilson Marques, Genomics England Research Consortium, Joseph Shaw, James Polke, Ettore Salsano, Silvia Fenu, Davide Pareyson, Chiara Pisciotta, George K. Tofaris, Andrea H. Nemeth, John Ealing, Aleksandar Radunovic, Seamus Kearney, Kishore R. Kumar, Ste...
Source: Brain - November 16, 2023 Category: Neurology Source Type: research
