Clinical Phenotypes Associated With Cerebral Small Vessel Disease: An Overview of Systematic Reviews.

BACKGROUND AND OBJECTIVES: Cerebral small vessel disease (cSVD) causes lacunar and hemorrhagic stroke and is an important contributor to vascular cognitive impairment. Other potential physical and psychological consequences of cSVD have been described across various body systems. Descriptions of cSVD are available in journals specific to those individual body systems, but a comprehensive assessment of clinical manifestations across this disparate literature is lacking. We conducted an overview of systematic reviews describing clinical cSVD phenotypes. METHODS: We searched multidisciplinary databases from inception to December 2023. We included reviews describing concurrent clinical phenotypes in individuals with neuroimaging evidence of cSVD, defined using the STandards for ReportIng Vascular changes on nEuroimaging criteria. We broadly classified phenotypes into cognitive, mood and neuropsychiatric, respiratory, cardiovascular, renal-urinary, peripheral nervous system, locomotor, and gastrointestinal. We included both studies assessing multiple cSVD features and studies examining individual cSVD markers. We extracted risk factor-adjusted effect estimates, where possible, and assessed methodologic quality using the Assessment of Multiple Systematic Reviews-2 tool. RESULTS: After screening 6,156 publications, we included 24 systematic reviews reporting on 685 original studies and 1,135,943 participants. Cognitive and neuropsychiatric phenotypes were examined most often, particularly in relation to white matter hyperintensities (range of risk ratios [RRs] for cognitive phenotypes 1.21-1.49, range of 95% CI 1.01-1.84; for neuropsychiatric, RR 1.02-5.71, 95% CI 0.96-19.69). Two reviews focused solely on perivascular spaces. No reviews assessed lacunes or small subcortical infarcts separately from other cSVD features. Reviews on peripheral nervous system, urinary, or gastrointestinal phenotypes were lacking. Fourteen reviews had high methodologic quality, 5 had moderate quality, and 5 had low quality. Heterogeneity in cSVD definitions and phenotypic assessments was substantial. DISCUSSION: Neuroimaging markers of cSVD are associated with various clinical manifestations, suggesting a multisystem phenotype. However, features classically associated with cSVD, for example, gait, had limited supporting evidence, and for many body systems, there were no available reviews. Similarly, while white matter hyperintensities were relatively well studied, there were limited data on phenotypes associated with other cSVD features. Future studies should characterize the full clinical spectrum of cSVD and explore clinical associations beyond neurocognitive and neuropsychiatric presentations.

Imaging Biomarkers of VCI: A Focused Update.

Vascular cognitive impairment is common after stroke, in memory clinics, medicine for the elderly services, and undiagnosed in the community. Vascular disease is said to be the second most common cause of dementia after Alzheimer disease, yet vascular dysfunction is now known to predate cognitive decline in Alzheimer disease, and most dementias at older ages are mixed. Neuroimaging has a major role in identifying the proportion of vascular versus other likely pathologies in patients with cognitive impairment. Here, we aim to provide a pragmatic but evidence-based summary of the current state of potential imaging biomarkers, focusing on magnetic resonance imaging and computed tomography, which are relevant to diagnosing, estimating prognosis, monitoring vascular cognitive impairment, and incorporating our own experiences. We focus on markers that are well-established, with a known profile of association with cognitive measures, but also consider more recently described, including quantitative tissue markers of vascular injury. We highlight the gaps in accessibility and translation to more routine clinical practice.

Effectiveness and Cost-Effectiveness of Self-Management Interventions for Adults Living with Heart Failure to Improve Patient-Important Outcomes: An Evidence Map of Randomized Controlled Trials.

Self-management interventions (SMIs) may enhance heart failure (HF) outcomes and address challenges associated with disease management. This study aims to review randomized evidence and identify knowledge gaps in SMIs for adult HF patients. Within the COMPAR-EU project, from 2010 to 2018, we conducted searches in the databases MEDLINE, CINAHL, Embase, Cochrane, and PsycINFO. We performed a descriptive analysis using predefined categories and developed an evidence map of randomized controlled trials (RCTs). We found 282 RCTs examining SMIs for HF patients, comparing two to four interventions, primarily targeting individual patients (97%) globally (34 countries, only 31% from an European country). These interventions involved support techniques such as information sharing (95%) and self-monitoring (62%), often through a mix of in-person and remote sessions (43%). Commonly assessed outcomes included quality of life, hospital admissions, mortality, exercise capacity, and self-efficacy. Few studies have focused on lower socio-economic or minority groups. Nurses (68%) and physicians (30%) were the primary providers, and most studies were at low risk of bias in generating a random sequence for participant allocation; however, the reporting was noticeably unclear of methods used to conceal the allocation process. Our analysis has revealed prevalent support techniques and delivery methods while highlighting methodological challenges. These findings provide valuable insights for researchers, clinicians, and policymakers striving to optimize SMIs for individuals living with HF.

Self-management interventions for adults living with obesity to improve patient-relevant outcomes: An evidence map.

OBJECTIVES: To conduct an evidence map on self-management interventions and patient-relevant outcomes for adults living with overweight/obesity. METHODS: Following Arksey and O'Malley methodology, we searched in five electronical databases including randomized controlled trials (RCTs) on SMIs for overweight/obesity. We used the terms "self-management", "adult" and "obesity" for content. Two independent reviewers assessed eligible references; one reviewer extracted data, a second checked accuracy. RESULTS: We identified 497 RCTs (58% US, 20% Europe) including 99,741 (median 112, range 11-5145) adults living with overweight/obesity. Most research evaluated clinical outcomes (617, 55%) and behaviors adherence (255, 23%). Empowerment skills, quality of life and satisfaction were less targeted (8%, 7%, 0.2%, respectively). The most frequent techniques included sharing information (858, 99%), goal setting (619, 72%) and self-monitoring training (614, 71%), provided face-to-face (386, 45%) or in combination with remote techniques (256, 30%). Emotional management, social support and shared-decision were less frequent (18%, 26%, 4%). Socio-economic status, minorities or health literacy were seldom reported. CONCLUSION: There is a need of widening the scope of research by focusing on outcomes important to patients, assessing emotional/social/share-decision support, exploring remote techniques and including vulnerable populations.

Using a Taxonomy to Systematically Identify and Describe Self-Management Interventions Components in Randomized Trials for COPD.

Self-management interventions (SMIs) may improve outcomes in Chronic Obstructive Pulmonary Disease (COPD). However, accurate comparisons of their relative effectiveness are challenging, partly due to a lack of clarity and detail regarding the intervention content being evaluated. This study systematically describes intervention components and characteristics in randomized controlled trials (RCTs) related to COPD self-management using the COMPAR-EU taxonomy as a framework, identifying components that are insufficiently incorporated into the design of the intervention or insufficiently reported. Overall, 235 RCTs published between 2010 and 2018, from a systematic review were coded using the taxonomy, which includes 132 components across four domains: intervention characteristics, expected patient (or caregiver) self-management behaviours, patient relevant outcomes, and target population characteristics. Risk of bias was also assessed. Interventions mainly focused on physical activity (67.4%), and condition-specific behaviours like breathing exercise (63.5%), self-monitoring (50.8%), and medication use (33.9%). Support techniques like education and skills-training, self-monitoring, and goal setting (over 35% of the RCTs) were mostly used for this. Emotional-based techniques, problem-solving, and shared decision-making were less frequently reported (less than 15% of the studies). Numerous SMIs components were insufficiently incorporated into the design of COPD SMIs or insufficiently reported. Characteristics like mode of delivery, intensity, location, and providers involved were often not described. Only 8% of the interventions were tailored to the target population's characteristics. Outcomes that are considered important by patients were hardly taken into account. There is still a lot to improve in both the design and description of SMIs for COPD. Using a framework such as the COMPAR-EU SMI taxonomy may contribute to better reporting and to better informing of replication efforts. In addition, prospective use of the taxonomy for developing and reporting intervention content would further aid in building a cumulative science of effective SMIs in COPD.

Investigating secondary white matter degeneration following ischemic stroke by modelling affected fiber tracts.

Secondary white matter degeneration is a common occurrence after ischemic stroke, as identified by Diffusion Tensor Imaging (DTI). However, despite recent advances, the time course of the process is not completely understood. The primary aim of this study was to assess secondary degeneration using an approach whereby we create a patient-specific model of damaged fibers based on the volumetric characteristics of lesions. We also examined the effects of secondary degeneration along the modelled streamlines at different distances from the primary infarction using DTI. Eleven patients who presented with upper limb motor deficits at the time of a first-ever ischemic stroke were included. They underwent scanning at weeks 6 and 29 post-stroke. The fractional anisotropy (FA), mean diffusivity (MD), primary eigenvalue (λ1), and transverse eigenvalue (λ23) were measured. Using regions of interest based on the simulation output, the differences between the modelled fibers and matched contralateral areas were analyzed. The longitudinal change between the two time points and across five distances from the primary lesion was also assessed using the ratios of diffusion quantities (rFA, rMD, rλ1, and rλ23) between the ipsilesional and contralesional hemisphere. At week 6 post-stroke, significantly decreased λ1 was found along the ipsilesional corticospinal tract (CST) with a trend towards lower FA, reduced MD and λ23. At week 29 post-stroke, significantly decreased FA was shown relative to the non-lesioned side, with a trend towards lower λ1, unchanged MD, and higher λ23. Along the ipsilesional tract, the rFA diminished, whereas the rMD, rλ1, and rλ23 significantly increased over time. No significant variations in the time progressive effect with distance were demonstrated. The findings support previously described mechanisms of secondary degeneration and suggest that it spreads along the entire length of a damaged tract. Future investigations using higher-order tractography techniques can further explain the intravoxel alterations caused by ischemic injury.

Imaging markers of intracranial aneurysm development: A systematic review.

BACKGROUND: Imaging markers of intracranial aneurysm (IA) development are not well established. PURPOSE: To provide an overview of imaging markers of IA development. METHODS: A systematic search of PubMed and Embase up to December 1st 2020 using predefined criteria. Thirty-six studies met our inclusion criteria. We performed a quantitative summary of the included studies. RESULTS: We found converging evidence for A1 segment asymmetry as an anatomical marker of anterior communicating artery (Acom) aneurysm development, and moderate evidence for several other markers. No hemodynamic markers yielded converging or moderate evidence. There was large heterogeneity across studies, especially in the definitions of imaging markers and study outcomes used. Due to the poor methodological quality of many studies and unavailability of effect sizes or crude data to calculate effect sizes, a formal meta-analysis was not possible. CONCLUSIONS: We only identified A1 segment asymmetry as an imaging marker of Acom aneurysm development with converging evidence. A meta-analysis was not possible due to the heterogeneity of marker definitions and outcomes used, and poor methodological quality of many studies. Future studies should use robust study designs and uniformly defined imaging markers and outcome measures.

Post-stroke cognitive impairment on the Mini-Mental State Examination primarily relates to left middle cerebral artery infarcts.

BACKGROUND: Post-stroke cognitive impairment can occur after damage to various brain regions, and cognitive deficits depend on infarct location. The Mini-Mental State Examination (MMSE) is still widely used to assess post-stroke cognition, but it has been criticized for capturing only certain cognitive deficits. Along these lines, it might be hypothesized that cognitive deficits as measured with the MMSE primarily involve certain infarct locations. AIMS: This comprehensive lesion-symptom mapping study aimed to determine which acute infarct locations are associated with post-stroke cognitive impairment on the MMSE. METHODS: We examined associations between impairment on the MMSE (<5th percentile; normative data) and infarct location in 1198 patients (age 67 ± 12 years, 43% female) with acute ischemic stroke using voxel-based lesion-symptom mapping. As a frame of reference, infarct patterns associated with impairments in individual cognitive domains were determined, based on a more detailed neuropsychological assessment. RESULTS: Impairment on the MMSE was present in 420 patients (35%). Large voxel clusters in the left middle cerebral artery territory and thalamus were significantly (p < 0.01) associated with cognitive impairment on the MMSE, with highest odds ratios (>15) in the thalamus and superior temporal gyrus. In comparison, domain-specific impairments were related to various infarct patterns across both hemispheres including the left medial temporal lobe (verbal memory) and right parietal lobe (visuospatial functioning). CONCLUSIONS: Our findings indicate that post-stroke cognitive impairment on the MMSE primarily relates to infarct locations in the left middle cerebral artery territory. The MMSE is apparently less sensitive to cognitive deficits that specifically relate to other locations.