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Sickle cell disease (SCD) is the most common type of hereditary anaemia and genetic disorder worldwide. Cerebrovascular disease is one of its most devastating complications, with consequent increased morbidity and mortality. Current guidelines suggest that children and adults with SCD who develop acute ischaemic stroke should be transfused without delay. Those with acute ischaemic stroke aged over 18 years who present within 4.5 hours of symptom onset should be considered for intravenous thrombolysis; older patients with conventional vascular risk factors are the most likely to benefit. Endovascular thrombectomy should be considered carefully in adults with SCD as there are few data to guide how the prevalence of cerebral vasculopathy may confound the expected benefits or risks of intervention. We present a practical approach to cerebrovascular disease in sickle cell patients based on the available evidence and our experience.

Spontaneous spinal cord infarction is significantly less common than cerebrovascular disease. Because of the tight anatomical distribution of pathways in the cord, small spinal cord infarcts usually give more obvious symptoms and signs than similar lesions in the brain. Large epidemiological stroke studies have generally not included spinal cord stroke and so the incidence of vascular syndromes in the spinal cord is unknown. Management and prevention strategies for spontaneous spinal cord infarcts stem from small case series and case reports. Patient outcomes from spinal cord infarction are better with prompt recognition, timely management and prevention of associated medical complications arising from paraplegia, tetraplegia, neurogenic bladder and bowel dysfunction. The process of rehabilitation following spinal cord infarction is an evolving area.

Cerebral small vessel disease (SVD) causes lacunar stroke and vascular cognitive impairment in older people. The pathogenic pathways from vessel pathology to parenchymal damage in SVD are unknown. Neurofilaments are axonal structural proteins. Neurofilament-light (NfL) is an emerging biomarker for neurological disease. Here, we examined the high molecular weight form neurofilament-heavy (NfH) and quantified a characteristic pattern of peri-arterial (vasculocentric) NfH labeling. Subcortical frontal and parietal white matter from young adult controls, aged controls, and older people with SVD or severe Alzheimer disease (n = 52) was immunohistochemically labeled for hyperphosphorylated NfH (pNfH). The extent of pNfH immunolabeling and the degree of vasculocentric axonal pNfH were quantified. Axonal pNfH immunolabeling was sparse in young adults but a common finding in older persons (controls, SVD, or AD). Axonal pNfH was often markedly concentrated around small penetrating arteries. This vasculocentric feature was more common in older people with SVD than in those with severe AD (p = 0.004). We conclude that axonal pNfH is a feature of subcortical white matter in aged brains. Vasculocentric axonal pNfH is a novel parenchymal lesion that is co-located with SVD arteriopathy and could be a consequence of vessel pathology.

Cerebral small vessel disease (SVD) is common in older people and is associated with lacunar stroke, white matter hyperintensities (WMH) and vascular cognitive impairment. Cerebral blood flow (CBF) is reduced in SVD, particularly within white matter.Here we quantified test–retest reliability in CBF measurements using pseudo-continuous arterial spin labelling (pCASL) in older adults with clinical and radiological evidence of SVD (N=54, mean (SD): 66.9 (8.7) years, 15 females/39 males). We generated whole-brain CBF maps on two visits at least 7 days apart (mean (SD): 20 (19), range 7-117 days).Test–retest reliability for CBF was high in all tissue types, with intra-class correlation coefficient [95%CI]: 0.758 [0.616, 0.852] for whole brain, 0.842 [0.743, 0.905] for total grey matter, 0.771 [0.636, 0.861] for deep grey matter (caudate-putamen and thalamus), 0.872 [0.790, 0.923] for normal-appearing white matter (NAWM) and 0.780 [0.650, 0.866] for WMH (all pWe conclude that pCASL has high test–retest reliability as a quantitative measure of CBF in older adults with SVD. These findings support the use of pCASL in routine clinical imaging and as a clinical trial endpoint.All data come from the PASTIS trial, prospectively registered at: https://eudract.ema.europa.eu (2015-001235-20, registered 13/05/2015), http://www.clinicaltrials.gov (NCT02450253, registered 21/05/2015).

The COVID-19 pandemic has resulted in periods of remote working for some junior doctors, due to shielding and clinical vulnerability. This report offers practical guidance for junior doctors and their supervisors on how to make a period of remote working safe and effective, while maintaining education, training progression and morale. We outline specific challenges and practicalities that should be considered prior to commencing remote working and discuss what tasks and activities are best suited to a remote-working junior doctor. We offer a positive outlook that, with adequate support, a junior doctor can continue to progress in their training while working remotely, and can make a period of remote working an opportunity for personal and professional development while remaining an effective and valuable member of the clinical team.

Introduction\ud There are few randomized clinical trials in vascular cognitive impairment (VCI). This trial tested the hypothesis that the PDE5 inhibitor tadalafil, a widely used vasodilator, increases cerebral blood flow (CBF) in older people with symptomatic small vessel disease, the main cause of VCI.\ud \ud Methods\ud In a double-blind, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥7 days apart (randomized to order of treatment). The primary endpoint, change in subcortical CBF, was measured by arterial spin labelling.\ud \ud Results\ud Tadalafil increased CBF non-significantly in all subcortical areas (N = 55, age: 66.8 (8.6) years) with greatest treatment effect within white matter hyperintensities (+9.8%, P = .0960). There were incidental treatment effects on systolic and diastolic blood pressure (–7.8, –4.9 mmHg; P < .001). No serious adverse events were observed.\ud \ud Discussion\ud This trial did not identify a significant treatment effect of single-administration tadalafil on subcortical CBF. To detect treatment effects may require different dosing regimens.