Association of Cerebrovascular Reactivity With 1-Year Imaging and Clinical Outcomes in Small Vessel Disease: An Observational Cohort Study.

Background And Objectives: In patients with cerebral small vessel disease (SVD), impaired cerebrovascular reactivity (CVR) is related to worse concurrent SVD burden, but less is known about cerebrovascular reactivity and long-term SVD lesion progression and clinical outcomes. We investigated associations between cerebrovascular reactivity and 1-year progression of SVD features and clinical outcomes.

Methods: Between 2018 and 2021, we recruited patients from the Edinburgh/Lothian stroke services presenting with minor ischemic stroke and SVD features as part of the Mild Stroke Study 3, a prospective observational cohort study (ISRCTN 12113543).

Assessing the extent and determinants of socioeconomic inequalities in epilepsy in the UK: a systematic review and meta-analysis of evidence.

Background: Socioeconomic inequalities in epilepsy incidence and its adverse outcomes are documented internationally, yet the extent of inequalities and factors influencing the association can differ between countries. A UK public health response to epilepsy, which prevents epilepsy without widening inequalities, is required. However, the data on UK epilepsy inequalities have not been synthesised in a review and the underlying determinants are unknown.

p-tau Ser356 is associated with Alzheimer's disease pathology and is lowered in brain slice cultures using the NUAK inhibitor WZ4003.

Tau hyperphosphorylation and aggregation is a common feature of many dementia-causing neurodegenerative diseases. Tau can be phosphorylated at up to 85 different sites, and there is increasing interest in whether tau phosphorylation at specific epitopes, by specific kinases, plays an important role in disease progression. The AMP-activated protein kinase (AMPK)-related enzyme NUAK1 has been identified as a potential mediator of tau pathology, whereby NUAK1-mediated phosphorylation of tau at Ser356 prevents the degradation of tau by the proteasome, further exacerbating tau hyperphosphorylation and accumulation.

Imaging incidence and type in primary care patients with low back pain: a cross-sectional study on new referrals to an Australian specialist spinal surgical centre.

Introduction Low back pain (LBP) is common and a significant cause of morbidity. Many patients receive inappropriate imaging for LBP in primary care. Aim To explore the incidence and type of spinal imaging conducted for LBP patients referred from general practice for specialist surgical opinion, and evaluate whether imaging conformed to clinical guidelines.

Longitudinal Changes of White Matter Hyperintensities in Sporadic Small Vessel Disease: A Systematic Review and Meta-analysis.

Background And Objectives: White matter hyperintensities (WMHs) are frequent imaging features of small vessel disease (SVD) and related to poor clinical outcomes. WMH progression over time is well described, but regression was also noted recently, although the frequency and associated factors are unknown. This systematic review and meta-analysis aims to assess longitudinal intraindividual WMH volume changes in sporadic SVD.

Impact of Small Vessel Disease Progression on Long-term Cognitive and Functional Changes After Stroke.

Background And Objectives: The severity of white matter hyperintensities (WMH) at presentation with stroke is associated with poststroke dementia and dependency. However, WMH can decrease or increase after stroke; prediction of cognitive decline is imprecise; and there are few data assessing longitudinal interrelationships among changing WMH, cognition, and function after stroke, despite the clinical importance.

Methods: We recruited patients within 3 months of a minor ischemic stroke, defined as NIH Stroke Scale (NIHSS) score <8 and not expected to result in a modified Rankin Scale (mRS) score >2.

11β-Hydroxylase (CYP11B1) gene variants and new-onset depression in later life.

Background: Cumulative exposure to high glucocorticoid levels is detrimental for the brain and may have particular implications in later life. A feature of late-life depression is increased cortisol secretion. Variants in the CYP11B1 gene, which codes for the enzyme responsible for cortisol synthesis, could influence risk of late-life depression, but this hypothesis has not been examined.

Scan-Negative Cauda Equina Syndrome: A Prospective Cohort Study.

Objective: To describe clinical features relevant to diagnosis, mechanism, and etiology in patients with "scan-negative" cauda equina syndrome (CES).

Methods: We carried out a prospective study of consecutive patients presenting with the clinical features of CES to a regional neurosurgery center comprising semi-structured interview and questionnaires investigating presenting symptoms, neurologic examination, psychiatric and functional disorder comorbidity, bladder/bowel/sexual function, distress, and disability.

Results: A total of 198 patients presented consecutively over 28 months.

Relationship Between Venules and Perivascular Spaces in Sporadic Small Vessel Diseases.

Background and Purpose- Perivascular spaces (PVS) around venules may help drain interstitial fluid from the brain. We examined relationships between suspected venules and PVS visible on brain magnetic resonance imaging. Methods- We developed a visual venular quantification method to examine the spatial relationship between venules and PVS.

Outcome Measures for Functional Neurological Disorder: A Review of the Theoretical Complexities.

The development and selection of optimal outcome measures is increasingly recognized as a key component of evidence-based medicine, particularly the need for the development of a standardized set of measures for use in clinical trials. This process is particularly complex for functional neurological disorder (FND) for several reasons. FND can present with a wide range of symptoms that resemble the full spectrum of other neurological disorders.

Preventing foot ulceration in diabetes: systematic review and meta-analyses of RCT data.

Aims/hypothesis: Foot ulceration is a serious complication for people with diabetes that results in high levels of morbidity for individuals and significant costs for health and social care systems. Nineteen systematic reviews of preventative interventions have been published, but none provides a reliable numerical summary of treatment effects. The aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to make the best possible use of the currently available data.

Predisposing Risk Factors for Functional Limb Weakness: A Case-Control Study.

Objective: Functional limb weakness is a common symptom of functional neurological disorder. Few controlled studies have examined possible predisposing factors to determine their specificity for this symptom.

Methods: In this prospective case-control study, patients with functional limb weakness (<2 years duration, N=107) were compared with a control group (comprising patients with weakness attributable to neurological disease, N=46, and healthy individuals, N=39).

Incident Cerebral Microbleeds After Intracerebral Hemorrhage.

Background and Purpose- The frequency and prognostic implications of incident cerebral microbleeds (CMB), defined as development of one or more new CMB, after intracerebral hemorrhage (ICH) is unclear. Therefore, we performed a systematic review and meta-analysis to investigate the frequency and prognostic implications of incident CMB after ICH. Methods- We searched Ovid Medline and Embase in May 2018 for longitudinal studies of adults who underwent brain magnetic resonance imaging at 2 or more times after ICH.

Hiding in Plain Sight: Functional Neurological Disorders in the News.

Objective: Functional movement and seizure disorders are still widely misunderstood and receive little public and academic attention. This is in stark contrast to their high prevalence and levels of associated disability. In an exploratory observational study, the authors examined whether the relative lack of media coverage of functional neurological disorders is in part due to misidentification in "human interest" news stories.

The development and validation of a multivariable prognostic model to predict foot ulceration in diabetes using a systematic review and individual patient data meta-analyses.

Aims: Diabetes guidelines recommend screening for the risk of foot ulceration but vary substantially in the underlying evidence base. Our purpose was to derive and validate a prognostic model of independent risk factors for foot ulceration in diabetes using all available individual patient data from cohort studies conducted worldwide.

Methods: We conducted a systematic review and meta-analysis of individual patient data from 10 cohort studies of risk factors in the prediction of foot ulceration in diabetes.

Revisited: A Systematic Review of Therapeutic Hypothermia for Adult Patients Following Traumatic Brain Injury.

Objectives: Therapeutic hypothermia has been of topical interest for many years and with the publication of two international, multicenter randomized controlled trials, the evidence base now needs updating. The aim of this systematic review of randomized controlled trials is to assess the efficacy of therapeutic hypothermia in adult traumatic brain injury focusing on mortality, poor outcomes, and new pneumonia.

Data Sources: The following databases were searched from January 1, 2011, to January 26, 2018: Cochrane Central Register of Controlled Trial, MEDLINE, PubMed, and EMBASE.

is associated with lacunar ischemic stroke and deep ICH: Meta-analyses among 21,500 cases and 40,600 controls.

Objective: To determine whether common variants in familial cerebral small vessel disease (SVD) genes confer risk of sporadic cerebral SVD.

Methods: We meta-analyzed genotype data from individuals of European ancestry to determine associations of common single nucleotide polymorphisms (SNPs) in 6 familial cerebral SVD genes (, , , , , and ) with intracerebral hemorrhage (ICH) (deep, lobar, all; 1,878 cases, 2,830 controls) and ischemic stroke (IS) (lacunar, cardioembolic, large vessel disease, all; 19,569 cases, 37,853 controls). We applied data quality filters and set statistical significance thresholds accounting for linkage disequilibrium and multiple testing.

White matter hyperintensity reduction and outcomes after minor stroke.

Objective: To assess factors associated with white matter hyperintensity (WMH) change in a large cohort after observing obvious WMH shrinkage 1 year after minor stroke in several participants in a longitudinal study.

Methods: We recruited participants with minor ischemic stroke and performed clinical assessments and brain MRI. At 1 year, we assessed recurrent cerebrovascular events and dependency and repeated the MRI.

Early life risk factors for cerebrovascular disease: A systematic review and meta-analysis.

Objective: Cerebrovascular disease (CVD) causes subclinical brain vascular lesions detected using neuroimaging and childhood factors may increase later CVD risk.

Methods: We searched MEDLINE, PsycINFO, and EMBASE, and meta-analyzed all available evidence on childhood (premorbid) IQ, socioeconomic status (SES), education, and subclinical CVD in later life. Overall odds ratios (OR), mean difference or correlation, and 95% confidence intervals (CIs) were calculated using random effects methods.