Clinical features and prognostic factors in adults with viral meningitis
AbstractClinical features applicable to the entire spectrum of viral meningitis are limited, and prognostic factors for adverse outcomes are undetermined.This nationwide population-based prospective cohort study included all adults with presumed and microbiologically confirmed viral meningitis in Denmark from 2015 until 2020. Prognostic factors for an unfavourable outcome (Glasgow Outcome Scale score of 1 –4) 30 days after discharge were examined by modified Poisson regression.In total, 1066 episodes of viral meningitis were included, yielding a mean annual incidence of 4.7 episodes per 100 000 persons. Pathogens were en...
Source: Brain - March 16, 2023 Category: Neurology Source Type: research
The Italian reappraisal of the most frequent genetic defects in hereditary optic neuropathies and the global top 10
Ministry of Health10.13039/501100003196GR-2016-02361449Emilia-Romagna Region10.13039/501100009879PRUa1RI-2012-008 (Source: Brain)
Source: Brain - March 13, 2023 Category: Neurology Source Type: research
Anoctamin-5 related muscle disease: clinical and genetic findings in a large European cohort
AbstractAnoctamin-5 related muscle disease is caused by biallelic pathogenic variants in the anoctamin-5 gene (ANO5) and shows variable clinical phenotypes: limb-girdle muscular dystrophy type 12 (LGMD-R12), distal muscular dystrophy type 3 (MMD3), pseudometabolic myopathy or asymptomatic hyperCKaemia.In this retrospective, observational, multicentre study we gathered a large European cohort of patients withANO5-related muscle disease to study the clinical and genetic spectrum and genotype –phenotype correlations.We included 234 patients from 212 different families, contributed by 15 centres from 11 European countries. T...
Source: Brain - March 13, 2023 Category: Neurology Source Type: research
Genetically identical twin-pair difference models support the amyloid cascade hypothesis
AbstractThe amyloid cascade hypothesis has strongly impacted the Alzheimer's disease research agenda and clinical trial designs over the past decades, but precisely how amyloid- β pathology initiates the aggregation of neocortical tau remains unclear. We cannot exclude the possibility of a shared upstream process driving both amyloid-β and tau in an independent manner instead of there being a causal relationship between amyloid-β and tau. Here, we tested the premise that if a causal relationship exists, then exposure should be associated with outcome both at the individual level as well as within identical twin-pairs, w...
Source: Brain - March 9, 2023 Category: Neurology Source Type: research
Multiomics and machine-learning identify novel transcriptional and mutational signatures in amyotrophic lateral sclerosis
AbstractAmyotrophic lateral sclerosis is a fatal and incurable neurodegenerative disease that mainly affects the neurons of the motor system. Despite the increasing understanding of its genetic components, their biological meanings are still poorly understood. Indeed, it is still not clear to which extent the pathological features associated with amyotrophic lateral sclerosis are commonly shared by the different genes causally linked to this disorder. To address this point, we combined multiomics analysis covering the transcriptional, epigenetic and mutational aspects of heterogenous human induced pluripotent stem cell-der...
Source: Brain - March 8, 2023 Category: Neurology Source Type: research
Moving, fast and slow: behavioural insights into bradykinesia in Parkinson ’s disease
AbstractThe debilitating symptoms of Parkinson ’s disease, including the hallmark slowness of movement, termed bradykinesia, were described more than 100 years ago. Despite significant advances in elucidating the genetic, molecular and neurobiological changes in Parkinson’s disease, it remains conceptually unclear exactly why patients with P arkinson’s disease move slowly. To address this, we summarize behavioural observations of movement slowness in Parkinson’s disease and discuss these findings in a behavioural framework of optimal control. In this framework, agents optimize the time it takes to gather and harves...
Source: Brain - March 2, 2023 Category: Neurology Source Type: research
Presymptomatic spinal muscular atrophy: a cautionary approach to the proposed new terminology
National Health and Medical Research Council of Australia10.13039/501100000925APP1194940 (Source: Brain)
Source: Brain - February 28, 2023 Category: Neurology Source Type: research
Molecular pathology and biomarker of progression in Alzheimer ’s disease
We know so much and yet we don ’t. What has been learnt about the complex molecular pathology of Alzheimer’s disease and its implications for treatment is without doubt impressive.1 –4 We now even have diagnostic CSF and plasma biomarkers based on this knowledge.5 Despite this, there is a sense of unease. Do we really understand the fundamental mechanisms that lead to cognitive decline in Alzheimer ’s disease or are we focusing on secondary processes, perhaps even epiphenomena? Time will tell but meanwhile this issue ofBrain presents some important new findings from three very different studies. These not only enla...
Source: Brain - July 29, 2022 Category: Neurology Source Type: research
How COVID-19 affects microvessels in the brain
This scientific commentary refers to ‘Neurovascular injury with complement activation and inflammation in COVID-19’ by Leeet al. (https://doi.org/10.1093/brain/awac151). (Source: Brain)
Source: Brain - July 15, 2022 Category: Neurology Source Type: research
Towards adaptive deep brain stimulation for freezing of gait
This scientific commentary refers to ‘Cortical phase-amplitude coupling is key to the occurrence and treatment of freezing of gait’ by Yinet al. (https://doi.org/10.1093/brain/awac121). (Source: Brain)
Source: Brain - July 15, 2022 Category: Neurology Source Type: research
Neurovascular injury with complement activation and inflammation in COVID-19
AbstractThe underlying mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to acute and long-term neurological manifestations remains obscure. We aimed to characterize the neuropathological changes in patients with coronavirus disease 2019 and determine the underlying pathophysiological mechanisms.In this autopsy study of the brain, we characterized the vascular pathology, the neuroinflammatory changes and cellular and humoral immune responses by immunohistochemistry.All patients died during the first wave of the pandemic from March to July 2020. All patients were adults who died after a ...
Source: Brain - July 5, 2022 Category: Neurology Source Type: research
Defective lipid signalling caused by mutations in PIK3C2B underlies focal epilepsy
AbstractEpilepsy is one of the most frequent neurological diseases, with focal epilepsy accounting for the largest number of cases. The genetic alterations involved in focal epilepsy are far from being fully elucidated.Here, we show that defective lipid signalling caused by heterozygous ultra-rare variants inPIK3C2B, encoding for the class II phosphatidylinositol 3-kinase PI3K-C2 β, underlie focal epilepsy in humans. We demonstrate that patients’ variants act as loss-of-function alleles, leading to impaired synthesis of the rare signalling lipid phosphatidylinositol 3,4-bisphosphate, resulting in mTORC1 hyperactivation....
Source: Brain - July 4, 2022 Category: Neurology Source Type: research
A deeper dive into top-down control of pain and itch
This scientific commentary refers to ‘Medullary kappa-opioid receptor neurons inhibit pain and itch through a descending circuit’ by Nguyenet al. (https://doi.org/10.1093/brain/awac189). (Source: Brain)
Source: Brain - June 30, 2022 Category: Neurology Source Type: research
Do genetic factors contribute to sex-specific differences in resilience to amyloid pathology?
This scientific commentary refers to ‘Sex differences in the genetic architecture of cognitive resilience to Alzheimer’s disease’ by Eissmanet al. (https://doi.org/10.1093/brain/awac177). (Source: Brain)
Source: Brain - June 21, 2022 Category: Neurology Source Type: research
Cortical phase-amplitude coupling is key to the occurrence and treatment of freezing of gait
AbstractFreezing of gait is a debilitating symptom in advanced Parkinson ’s disease and responds heterogeneously to treatments such as deep brain stimulation. Recent studies indicated that cortical dysfunction is involved in the development of freezing, while evidence depicting the specific role of the primary motor cortex in the multi-circuit pathology of freezing is lacking. Since abnormal beta-gamma phase-amplitude coupling recorded from the primary motor cortex in patients with Parkinson’s disease indicates parkinsonian state and responses to therapeutic deep brain stimulation, we hypothesized this metric might rev...
Source: Brain - June 15, 2022 Category: Neurology Source Type: research
