Journal of neurology, neurosurgery, and psychiatry
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J. Neurol. Neurosurg. Psychiatr. · Dec 2021
ReviewDiffusion and functional MRI findings and their relationship to behaviour in postconcussion syndrome: a scoping review.
Postconcussion syndrome (PCS) is a term attributed to the constellation of symptoms that fail to recover after a concussion. PCS is associated with a variety of symptoms such as headaches, concentration deficits, fatigue, depression and anxiety that have an enormous impact on patients' lives. There is currently no diagnostic biomarker for PCS. ⋯ Although some white matter and fMRI changes were correlated with cognitive or neuropsychiatric symptoms, there were no consistent, converging findings on the relationship between neuroimaging abnormalities and behavioural changes which could be largely due to the complex and heterogeneous presentation of PCS. Furthermore, the heterogeneity of symptoms in PCS may preclude discovery of one biomarker for all patients. Further research should take advantage of multimodal neuroimaging to better understand the brain-behaviour relationship, with a focus on individual differences rather than on group comparisons.
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J. Neurol. Neurosurg. Psychiatr. · Nov 2021
ReviewBlood-based high sensitivity measurements of beta-amyloid and phosphorylated tau as biomarkers of Alzheimer's disease: a focused review on recent advances.
Discovery and development of clinically useful biomarkers for Alzheimer's disease (AD) and related dementias have been the focus of recent research efforts. While cerebrospinal fluid and positron emission tomography or MRI-based neuroimaging markers have made the in vivo detection of AD pathology and its consequences possible, the high cost and invasiveness have limited their widespread use in the clinical setting. On the other hand, advances in potentially more accessible blood-based biomarkers had been impeded by lack of sensitivity in detecting changes in markers of the hallmarks of AD, including amyloid-β (Aβ) peptides and phosphorylated tau (P-tau). ⋯ In this focused review, we describe several emerging technologies, including immunoprecipitation-mass spectrometry (IP-MS), single molecule array and Meso Scale Discovery immunoassay platforms, and appraise the current literature arising from their use to identify plaques, tangles and other AD-associated pathology. While there is potential clinical utility in adopting these technologies, we also highlight the further studies needed to establish Aβ and P-tau as blood-based biomarkers for AD, including validation with existing large sample sets, new independent cohorts from diverse backgrounds as well as population-based longitudinal studies. In conclusion, the availability of sensitive and reliable measurements of Aβ peptides and P-tau species in blood holds promise for the diagnosis, prognosis and outcome assessments in clinical trials for AD.
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J. Neurol. Neurosurg. Psychiatr. · Nov 2021
ReviewIschaemic stroke in anticoagulated patients with atrial fibrillation.
Anticoagulation substantially reduces the risk of stroke in patients with atrial fibrillation (AF). However, recent studies have shown that up to 22%-36% of patients on anticoagulation will suffer an ischaemic stroke (IS). In this narrative review, we provide an overview of risk factors, mechanisms, management of acute IS and strategies for secondary prevention for patients with AF with stroke despite oral anticoagulation. ⋯ The identification of one or more possible mechanisms of stroke despite anticoagulation may allow for a more targeted and individualised approach for secondary prevention. There are limited data to guide management in such patients, and strategies to prevent recurrent strokes include strict risk factor control and therapies targeting the most likely stroke mechanism. In cases where AF is suspected to be the culprit, clinical trials are needed to test the safety and efficacy of left atrial appendage occlusion plus anticoagulation versus continued anticoagulation alone.
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J. Neurol. Neurosurg. Psychiatr. · Oct 2021
ReviewWilson's disease: update on pathogenesis, biomarkers and treatments.
Wilson's disease is an autosomal-recessive disorder of copper metabolism caused by mutations in ATP7B and associated with neurological, psychiatric, ophthalmological and hepatic manifestations. Decoppering treatments are used to prevent disease progression and reduce symptoms, but neurological outcomes remain mixed. In this article, we review the current understanding of pathogenesis, biomarkers and treatments for Wilson's disease from the neurological perspective, with a focus on recent advances. ⋯ We highlight limitations in our current approach to making a diagnosis and novel diagnostic biomarkers, including the potential for newborn screening programmes. We describe recent progress in developing imaging and wet (fluid) biomarkers for neurological involvement, including findings from quantitative MRI and other neuroimaging studies, and the development of a semiquantitative scoring system for assessing radiological severity. Finally, we cover the use of established and novel chelating agents, paradoxical neurological worsening, and progress developing targeted molecular and gene therapy for Wilson's disease, before discussing future directions for translational research.
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Glioblastoma (GB) is the most common and most malignant primary brain tumour in adults. Despite much effort, gold standard therapy has not changed since the introduction of adjuvant temozolomide in 2005 and prognosis remains poor. ⋯ In addition, our increased knowledge of the biology of GB has revealed more potential targets, especially in the field of immunotherapy, which has been successful in revolutionising treatment of other cancers. We review the current best practice for the treatment of GB and explore some of the more recent advances in GB management from both a surgical and molecular therapeutic perspective.