Lancet neurology
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Randomized Controlled Trial Multicenter Study
Effect of blood pressure-lowering agents on microvascular function in people with small vessel diseases (TREAT-SVDs): a multicentre, open-label, randomised, crossover trial.
Hypertension is the leading risk factor for cerebral small vessel disease. We aimed to determine whether antihypertensive drug classes differentially affect microvascular function in people with small vessel disease. ⋯ EU Horizon 2020 programme.
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Hereditary transthyretin (TTR) amyloid polyneuropathy is an autosomal dominant life-threatening disorder. TTR is produced mainly by the liver but also by the choroid plexus and retinal pigment epithelium. Detailed clinical characterisation, identification of clinical red flags for misdiagnosis, and use of biomarkers enable early diagnosis and treatment. ⋯ As none of the disease-modifying therapies can cross the blood-brain barrier, TTR deposition in the CNS, which can cause stroke and cognitive impairment, remains an important unaddressed issue. CRISPR-Cas9-based one-time TTR editing therapy is being investigated in a phase 1 clinical study. Identification of the earliest stages of pathogenesis in TTR variant carriers is a major challenge that needs addressing for optimal management.
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Randomized Controlled Trial
Intracranial pressure monitoring with and without brain tissue oxygen pressure monitoring for severe traumatic brain injury in France (OXY-TC): an open-label, randomised controlled superiority trial.
Optimisation of brain oxygenation might improve neurological outcome after traumatic brain injury. The OXY-TC trial explored the superiority of a strategy combining intracranial pressure and brain tissue oxygen pressure (PbtO2) monitoring over a strategy of intracranial pressure monitoring only to reduce the proportion of patients with poor neurological outcome at 6 months. ⋯ The French National Program for Clinical Research, La Fondation des Gueules Cassées, and Integra Lifesciences.
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Neurodegenerative disorders, including Alzheimer's disease, are associated with microgliosis. Microglia have long been considered to have detrimental roles in Alzheimer's disease. However, functional analyses of genes encoding risk factors that are linked to late-onset Alzheimer's disease, and that are enriched or exclusively expressed in microglia, have revealed unexpected protective functions. ⋯ Several anti-TREM2 antibodies are in early clinical trials, and current efforts aim to achieve more efficient transport of these antibodies across the blood-brain barrier. PET imaging could be used to monitor target engagement. Data from animal models, and biomarker studies in patients, further support a rationale for boosting TREM2 functions during the preclinical stage of Alzheimer's disease.