Circadian Biology and the Neurovascular Unit.

Mammalian physiology and cellular function are subject to significant oscillations over the course of every 24-hour day. It is likely that these daily rhythms will affect function as well as mechanisms of disease in the central nervous system. In this review, we attempt to survey and synthesize emerging studies that investigate how circadian biology may influence the neurovascular unit. We examine how circadian clocks may operate in neural, glial, and vascular compartments, review how circadian mechanisms regulate cell-cell signaling, assess interactions with aging and vascular comorbidities, and finally ask whether and how circadian effects and disruptions in rhythms may influence the risk and progression of pathophysiology in cerebrovascular disease. Overcoming identified challenges and leveraging opportunities for future research might support the development of novel circadian-based treatments for stroke.

Mechanical Thrombectomy Workshops Improve Procedural Knowledge and Skills Among Neurointerventional Teams in Low- to Middle-Income Countries.

BACKGROUND: While mechanical thrombectomy (MT) is proven to be lifesaving and disability sparing, there remains a disparity in its access in low- to middle-income countries. We hypothesized that team-based MT workshops would improve MT knowledge and skills. METHODS: We designed a 22-hour MT workshop, conducted as 2 identical events: in English (Jamaica, January 2022) and in Spanish (Dominican Republic, May 2022). The workshops included participating neurointerventional teams (practicing neurointerventionalists, neurointerventional nurses, and technicians) focused on acute stroke due to large vessel occlusion. The course faculty led didactic and hands-on components, covering topics from case selection and postoperative management to device technology and MT surgical techniques. Attendees were evaluated on stroke knowledge and MT skills before and after the course using a multiple choice exam and simulated procedures utilizing flow models under fluoroscopy, respectively. Press conferences for public education with invited government officials were included to raise stroke awareness. RESULTS: Twenty-two physicians and their teams from 8 countries across the Caribbean completed the didactic and hands-on training. Overall test scores (n=18) improved from 67% to 85% (P<0.002). Precourse and postcourse hands-on assessments demonstrated reduced time to completion from 36.5 to 21.1 minutes (P<0.001). All teams showed an improvement in measures of good MT techniques, with 39% improvement in complete reperfusion. Eight teams achieved a Thrombolysis in Cerebral Infarction score of 3 on pre-course versus 15 of 18 teams on post-course. There was a significant reduction in total potentially dangerous maneuvers (70% pre versus 20% post; P<0.002). Universally, the workshop was rated as satisfactory and likely to change practice in 93% Dominican Republic and 75% Jamaica. CONCLUSIONS: A team-based hands-on simulation approach to MT training is novel, feasible, and effective in improving procedural skills. Participants viewed these workshops as practice-changing and instrumental in creating a pathway for increasing access to MT in low- to middle-income countries.

Cortical Spreading Depolarization in Moyamoya Vasculopathy: A Case Series.

BACKGROUND: Spreading depolarization describes a near-complete electrical discharge with altered local cerebral blood flow. It is described in association with acute and chronic diseases like hemorrhagic stroke or migraine. Moyamoya vasculopathy is a chronic, progressive cerebrovascular disorder leading to cerebral hypoperfusion, hemodynamically insufficient basal collateralization, and increased cortical microvascularization. METHODS: In a prospective case series, we monitored for spontaneous spreading depolarization activity by using intraoperative laser speckle imaging for real-time visualization and measurement of cortical perfusion and cerebrovascular reserve capacity during cerebral revascularization in 4 consecutive patients with moyamoya. RESULTS: Spontaneous spreading depolarization occurrence was documented in a patient with moyamoya before bypass grafting. Interestingly, this patient also exhibited a marked preoperative increase in angiographic collateral vessel formation. CONCLUSIONS: The spontaneous occurrence of SDs in moyamoya vasculopathy could potentially provide an explanation for localized cortical infarction and increased cortical microvascular density in these patients.

Overweight in Adolescence and Young Adulthood in Association With Adult Cerebrovascular Disease: The NFBC1966 Study.

BACKGROUND: Risk factors for cerebrovascular disease in adulthood are well known. However, research on individuals' risk factors throughout their life span has been limited. This prospective cohort study aims to determine the effect of body mass index (BMI) and its changes in adolescence and young adulthood on early onset cerebrovascular disease. METHODS: This study includes 10 491 people (5185 women) from the Northern Finland Birth Cohort 1966. Height, weight, and BMI were measured at ages 14 and 31 years. Sex- and age-specific BMI ranges were used to define overweight and obesity. Data on ischemic and hemorrhagic cerebrovascular diseases between ages 14 and 54 years were extracted from national hospital and death registers. Cox proportion hazard models (95% CI) were used to estimate associations between BMI or its changes and cerebrovascular disease, while adjusting for sex, smoking, educational level, BMI at the other time point, and age at menarche for women. Additionally, sex-BMI interactions were calculated. RESULTS: A total of 452 individuals (4.7%) experienced cerebrovascular disease during the follow-up. The risk of ischemic cerebrovascular disease was increased for overweight women at ages 14 years (hazard ratio [HR], 2.49 [95% CI, 1.44-4.31]) and 31 years (HR, 2.13 [95% CI, 1.14-3.97]), as well as for obese women at ages 14 years (HR, 1.87 [95% CI, 0.76-4.58) and 31 years (HR, 2.67 [95% CI, 1.26-5.65]), with normal weight as the reference. These results were independent of earlier or later BMI. Similar associations were not found among men. The risk of hemorrhagic cerebrovascular disease was increased at age 31 years both among obese women (HR, 3.49 [95% CI, 1.13-10.7) and obese men (HR, 5.75 [95% CI, 1.43-23.1). The risk of any cerebrovascular disease related to overweight at age 14 years was 2.09× higher among girls than boys (95% CI, 1.06-4.15). The risk of ischemic cerebrovascular disease related to obesity at age 31 years was 6.96× higher among women than men (95% CI, 1.36-35.7). CONCLUSIONS: Among women, being overweight in adolescence or young adulthood increases the risk of cerebrovascular disease, especially ischemic, independent of their earlier or later BMI.

Impact of Sleep Disorders and Disturbed Sleep on Brain Health: A Scientific Statement From the American Heart Association.

Accumulating evidence supports a link between sleep disorders, disturbed sleep, and adverse brain health, ranging from stroke to subclinical cerebrovascular disease to cognitive outcomes, including the development of Alzheimer disease and Alzheimer disease-related dementias. Sleep disorders such as sleep-disordered breathing (eg, obstructive sleep apnea), and other sleep disturbances, as well, some of which are also considered sleep disorders (eg, insomnia, sleep fragmentation, circadian rhythm disorders, and extreme sleep duration), have been associated with adverse brain health. Understanding the causal role of sleep disorders and disturbances in the development of adverse brain health is complicated by the common development of sleep disorders among individuals with neurodegenerative disease. In addition to the role of sleep disorders in stroke and cerebrovascular injury, mechanistic hypotheses linking sleep with brain health and biomarker data (blood-based, cerebrospinal fluid-based, and imaging) suggest direct links to Alzheimer disease-specific pathology. These potential mechanisms and the increasing understanding of the "glymphatic system," and the recognition of the importance of sleep in poststroke recovery, as well, support a biological basis for the indirect (through the worsening of vascular disease) and direct (through specific effects on neuropathology) connections between sleep disorders and brain health. Given promising evidence for the benefits of treatment and prevention, sleep disorders and disturbances represent potential targets for early treatment that may improve brain health more broadly. In this scientific statement, we discuss the evidence supporting an association between sleep disorders and disturbances and poor brain health ranging from stroke to dementia and opportunities for prevention and early treatment.

Cerebral dural arteriovenous fistulas in patients with PTEN-related hamartoma tumor syndrome.

Central nervous system (CNS) dural arteriovenous fistulas (DAVF) have been reported in PTEN-related hamartoma tumor syndrome (PHTS). However, PHTS-associated DAVF remain an underexplored field of the PHTS clinical landscape. Here, we studied cases with a PTEN pathogenic variant identified between 2007 and 2020 in our laboratory (n = 58), and for whom brain imaging was available. Two patients had DAVF (2/58, 3.4%), both presenting at advanced stages: a 34-year-old man with a left lateral sinus DAVF at immediate risk of hemorrhage, and a 21-year-old woman with acute intracranial hypertension due to a torcular DAVF. Interestingly, not all patients had 3D TOF/MRA, the optimal sequences to detect DAVF. Early diagnosis of DAVF can be lifesaving, and is easier to treat compared to developed, proliferative, or complex lesions. As a result, one should consider brain MRI with 3D TOF/MRA in PHTS patients at genetic diagnosis, with subsequent surveillance on a case-by-case basis.

Ambient air pollution, covert cerebrovascular disease and cognition: results from the ISSYS study.

BACKGROUND AND PURPOSE: Although air pollution (AP) has been associated with stroke and dementia, data regarding its relationship with covert cerebrovascular disease (cCVD) and cognition over time are sparse. The aim of this study was to explore these relationships. METHODS: A prospective population-based study of 976 stroke-free and non-demented individuals living in Barcelona, Spain, was conducted during 2010-2016. A land use regression model was used to estimate the exposure of each participant to AP: NOx, NO2, PM2.5, PM10, PMcoarse and PM2.5 absorbance. Cognitive function and cCVD were assessed at baseline (n = 976) and 4 years after (n = 317). Multivariate-adjusted models were developed. RESULTS: At baseline, 99 participants (10.1%) had covert brain infarcts and 91 (9.3%) had extensive periventricular white matter hyperintensities (WMHs). Marked subcortical WMH progression was seen in 19.7%; the incidence of other covert cerebrovascular lessons ranged between 5% and 6% each. PM2.5 was related to higher odds of having a covert brain infarct (odds ratio [OR] 2.21; 95% confidence interval [CI] 1.06-4.60). PM2.5 absorbance was related to higher odds of having extensive subcortical WMHs (OR 1.72; 95% CI 1.13-2.60), whereas NO2 was related to higher odds of having extensive subcortical (OR 1.66; 95% CI 1.17-2.35) or periventricular (OR 1.96; 95% CI 1.10-3.50) WMHs and to higher odds of developing marked subcortical WMH progression (OR 1.40; 95% CI 1.05-1.90). NOx was related to incident cerebral microbleeds (OR 1.36; 95% CI 1.04-1.79). There was no association between AP and cognition. CONCLUSIONS: Air pollutant predicts the presence and accumulation of cCVD. Its impact on cognitive impairment remains to be determined.

Impact of Stent Size Selection and Vessel Evaluation on Skull Base Cerebrovascular Diseases Treated With Willis Covered Stents: A Multicenter Retrospective Analysis.

PURPOSE: This study aimed to evaluate the impact of the diverse stent size selection on the clinical and angiographic outcomes of Willis covered stent (WCS) for the treatment of skull base cerebrovascular diseases. MATERIALS AND METHODS: A total of 147 patients with 151 skull base cerebrovascular diseases treated with WCS in 3 centers between January 2015 and July 2022 were included in this study. Several parameters depicting stent size and parent artery condition were incorporated into the analysis of the outcomes. RESULTS: Complete occlusion was found in 106 cases (68.2%) immediately after deployment and 126 cases (83.4%) after technical adjustment. In the multivariate logistics analysis, the difference between stent diameter and parent artery diameter (DD) was significantly associated with immediate endoleak without adjustment (odds ratio [OR]=0.410; p=0.005) and late endoleak (OR=0.275; p=0.028). In addition, differences between stent diameter and parent artery diameter at wide landing point (DSW) and differences between stent diameter and parent artery diameter at narrow landing point (DSN) was also was significant associated with immediate endoleak without adjustment and balloon re-dilation respectively. CONCLUSIONS: This study demonstrated that the diameter selection of the WCS was associated with the occurrence of endoleak during the treatment of skull base cerebrovascular diseases. Precise selection and evaluation of stent size and vessel condition were significant factors for skull base cerebrovascular diseases treated by WCS. CLINICAL IMPACT: This study demonstrates a significant association between the diameter selection of the Willis covered stent (WCS) and the occurrence of endoleak in the management of skull base cerebrovascular diseases. The results offer valuable medical evidence that can inform stent selection for WCS. The study emphasizes the significance of precise evaluation of stent size and vessel condition as crucial factors in WCS procedures. These findings underscore the importance of meticulous consideration and individualized approaches to stent selection, ultimately improving treatment outcomes in clinical practice.

Prevalence and 3-month follow-up of cerebrovascular MRI markers in hospitalized COVID-19 patients: the CORONIS study.

PURPOSE: To investigate the prevalence of cerebrovascular MRI markers in unselected patients hospitalized for COVID-19 (Coronavirus disease 2019), we compared these with healthy controls without previous SARS-CoV-2 infection or hospitalization and subsequently, investigated longitudinal (incidental) lesions in patients after three months. METHODS: CORONIS (CORONavirus and Ischemic Stroke) was an observational cohort study in adult hospitalized patients for COVID-19 and controls without COVID-19, conducted between April 2021 and September 2022. Brain MRI was performed shortly after discharge and after 3 months. Outcomes included recent ischemic (DWI-positive) lesions, previous infarction, microbleeds, white matter hyperintensities (WMH) and intracerebral hemorrhage and were analysed with logistic regression to adjust for confounders. RESULTS: 125 patients with COVID-19 and 47 controls underwent brain MRI a median of 41.5 days after symptom onset. DWI-positive lesions were found in one patient (1%) and in one (2%) control, both clinically silent. WMH were more prevalent in patients (78%) than in controls (62%) (adjusted OR: 2.95 [95% CI: 1.07-8.57]), other cerebrovascular MRI markers did not differ. Prevalence of markers in ICU vs. non-ICU patients was similar. After three months, five patients (5%) had new cerebrovascular lesions, including DWI-positive lesions (1 patient, 1.0%), cerebral infarction (2 patients, 2.0%) and microbleeds (3 patients, 3.1%). CONCLUSION: Overall, we found no higher prevalence of cerebrovascular markers in unselected hospitalized COVID-19 patients compared to controls. The few incident DWI-lesions were most likely to be explained by risk-factors of small vessel disease. In the general hospitalized COVID-19 population, COVID-19 shows limited impact on cerebrovascular MRI markers shortly after hospitalization.

The aneurysm occlusion and recurrence of posterior communicating artery aneurysms following the treatment with the pipeline embolization device.

Despite advancements in treatment modalities such as flow diverters, the optimal management of posterior communicating artery (PComA) aneurysms remains uncertain. While PComA aneurysms treated with the Pipeline Embolization Device (PED) has been reported, the characteristics and progression of incomplete occluded aneurysms remain unclear. Therefore, our study aims to investigate the occlusion status and recurrence rates of PComA aneurysms treated with PED. A retrospective review of consecutive PComA aneurysm patients treated with PED was conducted between January 2015 and December 2020. Only patients with radiological follow-up were included. PComA aneurysms were categorized into incomplete occlusion and complete occlusion group. The primary outcomes included the characteristics of incomplete occlusion at the follow-up angiography. Among 121 PComA aneurysms treated with PED at our institution, 80 aneurysms were eligible in our study. During the follow-up period, 19 (23.8%) aneurysms demonstrated incomplete occlusion. Notably, there were no instances of recurrence among the 80 followed-up cases. Baseline characteristics of patients and aneurysms were comparable between the groups with complete and incomplete occlusion. However, the incomplete occlusion group showed a lower rate of assisted coils embolization (21.2% vs. 55.7%, P = 0.017) and shorter median operative time (91.0 vs. 145.5 min, P = 0.039). Differences in functional outcomes, complications, and PComA occlusion status between the groups were not significant. Multivariate analysis revealed the use of coils was associated with lower odds of incomplete PComA aneurysm occlusion (OR 0.01, 95% CI 0.001-0.12; P = 0.001), while aneurysm size was associated with higher odds of incomplete occlusion (OR 1.25, 95% CI 1.10-1.46; P = 0.002). The treatment of PED for PComA aneurysm demonstrated favorable outcomes, with an acceptable rate of incomplete occlusion and no instances of recurrence observed. However, further research is needed to explore the optimal procedural strategy for large-sized PComA aneurysms.

Challenges and needs in cerebrovascular disease pathway: A qualitative descriptive study from the patients' and healthcare professionals' perspectives.

AIM(S): To understand patients' and healthcare professionals' experiences to improve care in and across different domains of the cerebrovascular disease pathway. DESIGN: A qualitative descriptive study. METHODS: Semi-structured in-person interviews were conducted among 22 patients diagnosed with acute cerebrovascular disease and 26 healthcare professionals taking care of them in a single tertiary-level hospital from August 2021 to March 2022. Data were analysed using deductive and inductive content analysis. The consolidated criteria for reporting qualitative research was used to ensure reliable reporting. RESULTS: Overall, 19 generic and 79 sub-categories describing perceived challenges with 17 generic and 62 sub-categories describing perceived needs were identified related to primary prevention, organization of stroke services, management of acute stroke, secondary prevention, rehabilitation, evaluation of stroke outcome and quality assessment, and life after stroke. CONCLUSION: Several challenges and needs were identified in and across the different domains of the cerebrovascular disease pathway. There is a requirement for adequate resources, early initiation of treatment, early diagnostics and recanalization, dedicated rehabilitation services, long-term counselling and support, and impact evaluation of services to improve cerebrovascular disease care. Future research on caregivers', and clinical leadership experiences in and across the cerebrovascular disease pathway is needed to explore the provision of services. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The results of this study can be applied by organizations, managers and research for developing and improving services in the cerebrovascular disease pathway. IMPACT: This study identified several patient-related, organizational and logistical needs and challenges, with suggestions for required actions, that can benefit the provision of effective, high-quality cerebrovascular disease care. REPORTING METHOD: We have adhered to relevant EQUATOR guidelines with the COREQ reporting method. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement.

Lateral Medullary Syndrome With Ipsilateral Upper Motor Neuron Facial Palsy.

Lateral medullary syndrome is a common presentation of posterior circulation ischemia that presents with ipsilateral Horner syndrome, ipsilateral facial numbness, contralateral body numbness, vestibular symptoms, ataxia, dysphagia, and dysarthria. Here, we describe an 84-year-old who presented to the hospital with right upper motor neuron facial weakness and gait abnormality found to have a right lateral medullary ischemic stroke. Multiple MRI's, including with thin brainstem slices, were without evidence of pontine, midbrain or cerebral ischemia outside the medulla. We postulate that the patient's ipsilateral upper motor neuron facial weakness was caused by involvement of aberrant corticobulbar fibers in the medulla ascending to the facial nucleus.

Walking forward or on hold: Could the ChatGPT be applied for seeking health information in neurosurgical settings?

Self-management is important for patients suffering from cerebrovascular events after neurosurgical procedures. An increasing number of artificial intelligence (AI)-assisted tools have been used in postoperative health management. ChatGPT is a new trend dialog-based chatbot that could be used as a supplemental tool for seeking health information. Responses from ChatGPT version 3.5 and 4.0 toward 13 questions raised by experienced neurosurgeons were evaluated in this exploratory study for their consistency and appropriateness blindly by the other three neurosurgeons. The readability of response text was investigated quantitively by word count and the Gunning Fog and Flesch-Kincaid indices. Results showed that the chatbot could provide relatively stable output between the two versions on consistency and appropriateness (χ² = 0.348). As for readability, there was a higher demand for readers to comprehend the output text in the 4.0 version (more counts of words; lower Flesch-Kincaid reading ease score; and higher Flesch-Kincaid grade level). In general, the capacity of ChatGPT to deliver effective health information is still under debate.

VasCog Screen test: sensitive in detecting cognitive impairment in patients who had a stroke or with heart failure.

INTRODUCTION: Vascular diseases, such as stroke and heart failure (HF), are associated with cognitive decline. Vascular cognitive impairment (CI) is commonly found in patients who had a stroke and with HF, ranging from mild CI to dementia. Early detection of CI is crucial for effective management and rehabilitation. This study aimed to develop the VasCog Screen test, a screening tool to detect CI in patients who had a stroke and with HF. METHOD: 427 patients who had a stroke and with HF were assessed using cognitive measures including Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and a formal neuropsychological battery. The short-MoCA was derived and combined with Symbol Digit Modalities Test (SDMT) to create the VasCog Screen. The discriminatory ability of different tests for CI was compared, establishing optimal cut-off points. Variants of short-MoCA including the SDMT were also evaluated. RESULTS: Similar prevalence rates of CI were found in stroke and HF cohorts. The most prevalent neuropsychological impairment was visuomotor speed, followed by visual memory and visuoconstruction. More than half of the patients were found to have CI. The VasCog Screen outperformed MMSE, MoCA and short-MoCA in detecting CI. The addition of SDMT to variants of the short-MoCA increased diagnostic accuracy. CONCLUSION: The VasCog Screen test offers a cognitive screening tool, which is sensitive to cognitive deficits characteristically found in patients who had a stroke and with HF. It was found to have good sensitivity, specificity and classification accuracy. It is easy to administer in busy clinics, enabling early detection of CI and facilitating appropriate interventions.

Effectiveness and safety of bridging therapy and endovascular therapy in patients with large cerebral infarctions: from ANGEL-ASPECT.

BACKGROUND AND PURPOSE: The benefits of thrombolytic therapy before endovascular thrombectomy in cases of acute ischaemic stroke, with a large infarction volume, remain unclear. This analysis aims to evaluate the effectiveness and safety of bridging therapy and endovascular therapy among patients with large cerebral infarctions. METHODS: In this post-hoc analysis of the multicentre prospective study of ANGEL-ASPECT (Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core), participants were divided into two groups: an endovascular therapy group and a bridging therapy group. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. The primary safety outcome was symptomatic intracranial haemorrhage. Ordinal logistic regression was performed to compare the primary endpoint between the two groups. Subgroup analyses were conducted to further explore potential risk factors associated with the outcomes. RESULTS: 122 patients were included, of whom 77 (63%) underwent endovascular therapy and 45 (37%) underwent bridging therapy. The median scores on mRS at 90 days of the bridging therapy group and the endovascular therapy group were 3 (2-5) and 4 (2-6), with no significant differences (common OR 1.36; 95% CI 0.71 to 2.61). Symptomatic intracranial haemorrhage was reported in three patients who were in the endovascular and bridging therapy groups (relative risk (RR) 1.71; 95% CI 0.36 to 8.12). The mortality between two groups did not differ (RR 0.75; 95% CI 0.37 to 1.54). CONCLUSIONS: Our study indicated that endovascular therapy alone might be a viable option for patients with large cerebral infarctions, displaying no noticeable disparity in outcomes compared with bridging therapy.

Paediatric intracranial dural arteriovenous fistulas: clinical characteristics, treatment outcomes and prognosis.

BACKGROUND: Compared with dural arteriovenous fistulas (DAVFs) in adult, paediatric DAVFs are notable for distinct clinical manifestations, low cure rate and poor prognosis. However, due to the limitations of small sample sizes, the long-term prognosis and follow-up data have not been described. METHODS: Clinical data from 43 consecutive paediatric DAVFs were documented and analysed between 2002 and 2022 at the author's institution. They were divided into infantile (Lasjaunias classification) and non-infantile (adult type and dural sinus malformation (DSM)) type DAVFs based on prognosis differences. RESULTS: Their mean age at first symptoms was 8.4±6.0 years. 29 boys and 14 girls presented between at birth and 18 years of age. 5 of 10 patients ≤1 year of age presented with asymptomatic cardiomegaly compared with 5/33 patients >1 year of age (p=0.022). 42 (88.4%) patients received endovascular treatment alone, while 9.3% underwent radiosurgery, burr hole embolisation or surgery. 28 (65.1%) patients experienced DAVF obliteration by the end of treatment. Among them, 26 cases underwent embolisation alone, one case had embolisation in conjunction with surgery, and one case underwent burr hole embolisation. The overall complication rate among patients was 9.3%, all resulting from endovascular treatment. According to the Lasjaunias Classification, there were 18 cases of adult type, 17 cases of infantile type and 8 cases of DSM. Compared with non-infantile-type DAVFs, infantile-type DAVFs showed more times of treatment, lower cure rate and worse prognosis (p<0.001, 0.003 and 0.021, respectively). The average follow-up duration was 41.4±36.2 months (3-228 months). 8 (22.9%) patients died. CONCLUSIONS: Most adult-type DAVFs and DSMs can now be effectively treated with embolisation, resulting in good outcomes and prognosis. However, there are still challenges in treating infantile-type DAVFs, and the prognosis is frequently poor.

Design of trials in lacunar stroke and cerebral small vessel disease: review and experience with the LACunar Intervention Trial 2 (LACI-2).

Cerebral small vessel disease (cSVD) causes lacunar stroke (25% of ischaemic strokes), haemorrhage, dementia, physical frailty, or is 'covert', but has no specific treatment. Uncertainties about the design of clinical trials in cSVD, which patients to include or outcomes to assess, may have delayed progress. Based on experience in recent cSVD trials, we reviewed ways to facilitate future trials in patients with cSVD.We assessed the literature and the LACunar Intervention Trial 2 (LACI-2) for data to inform choice of Participant, Intervention, Comparator, Outcome, including clinical versus intermediary endpoints, potential interventions, effect of outcome on missing data, methods to aid retention and reduce data loss. We modelled risk of missing outcomes by baseline prognostic variables in LACI-2 using binary logistic regression.Imaging versus clinical outcomes led to larger proportions of missing data. We present reasons for and against broad versus narrow entry criteria. We identified numerous repurposable drugs with relevant modes of action to test in various cSVD subtypes. Cognitive impairment is the most common clinical outcome after lacunar ischaemic stroke but was missing more frequently than dependency, quality of life or vascular events in LACI-2. Assessing cognitive status using Diagnostic and Statistical Manual for Mental Disorders Fifth Edition can use cognitive data from multiple sources and may help reduce data losses.Trials in patients with all cSVD subtypes are urgently needed and should use broad entry criteria and clinical outcomes and focus on ways to maximise collection of cognitive outcomes to avoid missing data.

Intelligent cholinergic white matter pathways algorithm based on U-net reflects cognitive impairment in patients with silent cerebrovascular disease.

BACKGROUND AND OBJECTIVE: The injury of the cholinergic white matter pathway underlies cognition decline in patients with silent cerebrovascular disease (SCD) with white matter hyperintensities (WMH) of vascular origin. However, the evaluation of the cholinergic white matter pathway is complex with poor consistency. We established an intelligent algorithm to evaluate WMH in the cholinergic pathway. METHODS: Patients with SCD with WMH of vascular origin were enrolled. The Cholinergic Pathways Hyperintensities Scale (CHIPS) was used to measure cholinergic white matter pathway impairment. The intelligent algorithm used a deep learning model based on convolutional neural networks to achieve WMH segmentation and CHIPS scoring. The diagnostic value of the intelligent algorithm for moderate-to-severe cholinergic pathway injury was calculated. The correlation between the WMH in the cholinergic pathway and cognitive function was analysed. RESULTS: A number of 464 patients with SCD were enrolled in internal training and test set. The algorithm was validated using data from an external cohort comprising 100 patients with SCD. The sensitivity, specificity and area under the curve of the intelligent algorithm to assess moderate and severe cholinergic white matter pathway injury were 91.7%, 87.3%, 0.903 (95% CI 0.861 to 0.952) and 86.5%, 81.3%, 0.868 (95% CI 0.819 to 0.921) for the internal test set and external validation set. for the. The general cognitive function, execution function and attention showed significant differences among the three groups of different CHIPS score (all p<0.05). DISCUSSION: We have established the first intelligent algorithm to evaluate the cholinergic white matter pathway with good accuracy compared with the gold standard. It helps more easily assess the cognitive function in patients with SCD.