Exploring vascular contributions to cognitive impairment and dementia (ENIGMA): protocol for a prospective observational study.

BACKGROUND: Post-stroke cognitive impairment (PSCI) is common. However, the underlying pathophysiology remains largely unknown. Understanding the role of microvascular changes and finding markers that can predict PSCI, could be a first step towards better screening and management of PSCI. Capillary dysfunction is a pathological feature of cerebral small vessel disease and may play a role in the mechanisms underlying PSCI. Extracellular vesicles (EVs) are secreted from cells and may act as disease biomarkers. We aim to investigate the role of capillary dysfunction in PSCI and the associations between EV characteristics and cognitive function one year after acute ischemic stroke (AIS) and transient ischemic attack (TIA). METHODS: The ENIGMA study is a single-centre prospective clinical observational study conducted at Aarhus University Hospital, Denmark. Consecutive patients with AIS and TIA are included and followed for one year with follow-up visits at three and 12 months. An MRI is performed at 24 h and 12 months follow-up. EV characteristics will be characterised from blood samples drawn at 24 h and three months follow-up. Cognitive function is assessed three and 12 months after AIS and TIA using the Repeatable Battery for the Assessment of Neuropsychological Status. DISCUSSION: Using novel imaging and molecular biological techniques the ENIGMA study will provide new knowledge about the vascular contributions to cognitive decline and dementia. TRIAL REGISTRATION: The study is retrospectively registered as an ongoing observational study at ClinicalTrials.gov with the identifier NCT06257823.

Diagnostic yield of computed tomography angiography in patients presenting with spontaneous intracerebral hemorrhage.

BACKGROUND: Hypertension and cerebral amyloid angiopathy are the most common causes of spontaneous intracerebral hemorrhage (ICH); however, these conditions do not imply macrovascular pathology. Still, computed tomography (CT) angiography (CTA) is often performed in the acute phase in patients with ICH. PURPOSE: To assess the diagnostic yield of CTA in the detection of secondary etiology in consecutive patients with spontaneous ICH. MATERIAL AND METHODS: We performed a retrospective analysis of data from a prospective single-center cohort study of 203 patients presenting with spontaneous ICH admitted to a comprehensive stroke center over a two-year period (15 October 2016 to 15 October 2018). The underlying vascular pathology was assessed using CTA. RESULTS: CTA was performed in addition to non-contrast CT and/or magnetic resonance imaging (MRI). Vascular pathology was found in 11 of 203 (5.4%) patients and included arteriovenous malformations (n=4), aneurysms (n=4), vasospasms (n=1), cerebral venous thrombosis (n=1), and other vascular malformations (n=1). In eight cases, the finding was deemed symptomatic. Patients with vascular pathology on CTA more often had lobar located hemorrhages (63.6% vs. 36.4%, P = 0.049). Numerically, patients with vascular pathology were younger, had smaller hematoma volumes, and lower mortality. CONCLUSION: Underlying macrovascular pathology was detected on CTA in only approximately 1 of 20 consecutive patients with ICH. The patients with vascular pathology more often had a hemorrhage with a lobar location and young age and the present study is supportive of a risk-based stratification approach in performing CTA.

Diffusional kurtosis imaging as a possible prognostic marker of cervical incomplete spinal cord injury outcome: a prospective pilot study.

BACKGROUND: Spinal cord injury (SCI) is associated with substantial chronic morbidity and mortality. Routine imaging techniques such as T1- and T2-weighted magnetic resonance imaging (MRI) are not effective in predicting neurological deficiency grade or outcome. Diffusional kurtosis imaging (DKI) is an MR imaging technique that provides microstructural information about biological tissue. There are no longitudinal prospective studies assessing DKI metrics in acute traumatic SCI. Therefore, the purpose of this study was to establish a DKI protocol for acute SCI and correlate the DKI metrics to the functional neurological outcome of the patients. METHODS: Eight consecutive SCI patients referred to our institution with cervical SCI were included in the study. An acute diagnostic MRI scan was supplemented with a novel fast, mean kurtosis DKI protocol, which describes the average deviation from Gaussian diffusional along nine different directions. Mean kurtosis values were measured at the injury site and normalized to the mean kurtosis values of a non-injured site. At discharge form specialized rehabilitation, patients were evaluated using the Spinal Cord Independence Measure-III (SCIM-III). The DKI metrics and SCIM-III were analysed using Spearman's rank correlation. RESULTS: This pilot study found a significant correlation between decreasing mean kurtosis values at the injury site of the spinal cord and higher grade of disability measured by the SCIM-III (p = 0.002). CONCLUSION: This pilot study found that DKI may be a valuable tool as a prognostic marker in the acute phase of SCI.

Cortical Atrophy, White Matter Lesions, and Bulb Configuration in Patients with Idiopathic Olfactory Loss and Other Causes of Olfactory Loss.

INTRODUCTION: While magnetic resonance imaging (MRI) is not included in the current guidelines for diagnosing olfactory disorders in the most recent position paper on olfactory dysfunction, both 1.5T and 3T MRI are commonly used in the diagnostic workup of many patients with olfactory loss. Often, MRI is used to rule out intracranial tumours, but other useful information may be obtained from MRI scans in these patients. The potential of MRI in olfactory loss depends on sufficient knowledge of structural changes in different aetiologies of olfactory loss. We present common clinical MRI findings in olfactory loss and evaluate the usefulness of structural integrity scores in differentiating between aetiologies. METHODS: In this study, we investigated if white matter hyperintensities (WMHs, measured by Fazekas score), global cortical atrophy (GCA), and medial temporal lobe atrophy (MTA) are more common in patients with idiopathic olfactory loss than in patients with acquired olfactory loss due to other aetiologies. Furthermore, we compared olfactory bulb (OB) configurations in different olfactory loss aetiologies. RESULTS: In 88 patients with olfactory loss, WMHs, GCA, and MTA were not more significant findings on MRI in idiopathic olfactory loss (n = 51) compared with other causes of acquired olfactory loss (Fazekas score p = 0.2977; GCA score p = 0.6748; MTA score p = 0.7851). Bulb configurations differed in patients suffering from post-traumatic olfactory loss and may aid in identifying the underlying aetiology in patients where trauma is among the suspected causes of olfactory loss. CONCLUSION: We recommend that structural MRI with an OB sequence is included in the diagnostic evaluation of olfactory loss with suspected congenital and post-traumatic aetiology and should be considered in idiopathic olfactory loss with suspected central aetiology (e.g., tumour).

Help-seeking behaviour and subsequent patient and system delays in stroke.

OBJECTIVES: Prehospital delay is the main reason why only a limited number of stroke patients receive reperfusion therapy. We aimed to investigate help-seeking behaviour in patients and bystanders after onset of stroke and subsequent patient and system delay. MATERIALS & METHODS: We conducted a cross-sectional study of 332 patients with stroke. We performed structured interviews and used data from the medical records and the Danish Stroke Registry. Primary outcomes were patient delay and system delay. RESULTS: The median patient delay was 280 min, and the median system delay was 97 min. For a patient delay of <3 h, an additional non-significant system delay of median 30 min was seen for a first contact to a general practitioner (GP), and an additional significant delay of median 490 min was seen for the small group of patients with a first contact to 'other' healthcare professionals compared to the Emergency Medical Services (EMS). For a patient delay of more than 3 h, an additional system delay of median 78 min was found when the first contact was directed to the out-of-hours primary care (OOH-PC). A total of 17% of patients were admitted to another hospital or department before arrival at the stroke centre; this resulted in a substantially prolonged system delay of a median of 431 min. CONCLUSIONS: Patient delay remains the main reason for delayed arrival at the stroke centre. Appropriate help-seeking behaviour and efficient pre-hospital triage are essential for reducing the prehospital delay and increasing the proportion of patients receiving reperfusion therapy.

Circulating DNA and frequency of colorectal cancer brain metastases in a presumed high-risk group.

This explorative prospective observational pilot study investigated if suggested risk factors, rectal cancer and lung metastases, could add to a relevant detection rate of asymptomatic brain metastases (BM) from colorectal cancer (CRC). Secondary, prognostic biological aspects were investigated by translational analysis of plasma samples. The study enrolled patients with rectal cancer and lung metastases. At inclusion, patients underwent a standard MRI scan of the brain. Cell-free DNA (cfDNA) level was measured by a direct fluorescence assay (DFA), and circulating tumor DNA (ctDNA) by ddPCR. BM was detected in one of twenty-nine included patients. Patients had higher cfDNA levels than healthy subjects (p < 0.01). Patients with the primary tumor in situ had higher cfDNA levels than those with resected primary tumor (p < 0.01). Patients with liver involvement had higher cfDNA levels (p = 0.12) and circulating tumor DNA levels (p = 0.01) than those without liver involvement. In conclusion, the modest incidence of BM does not justify routine MRI of the brain in this selected population. cfDNA by DFA could be a valuable tool when planning treatment and follow-up for CRC patients. Future studies should focus on identifying further characteristics and biomarkers associated with a high risk of BM, enhancing the possibility for early intervention.

Telehealth in Multidisciplinary Target Delineation for Radiotherapy During the COVID-19 Pandemic. A Review and a Case.

Like all other medical specialties, radiotherapy has been deeply influenced by the COVID-19 pandemic. The pandemic has had severe influence on the entire patient trajectory in oncology, from diagnosis to treatment and follow-up. Many examples of how to deal with patient and staff safety, shortness of staff and other resources and the quest to continue high-quality, evidence-based treatment have been presented. The use of telemedicine and telehealth is frequently presented as a part of the solution to overcome these challenges. Some of the available presented solutions will only apply in an acute, local setting, whereas others might inspire the community to improve quality and cost-effectiveness of radiotherapy as well as knowledge sharing in the future. Some of the unresolved issues in many of the available technical solutions are related to data security and public regulation, for example, GDPR (General Data Protection Regulation) in the EU and HIPAA compliance (Health Insurance Portability and Accountability Act) in the USA. Using a solution that involves a supplier's server in a non-EU country is problematic within the EU. In this paper we shortly review the influence of COVID-19 on radiotherapy. We describe some of the possible solutions for telehealth in target delineation - a crucial part of high-quality radiotherapy, which often requires multidisciplinary effort, hands-on corporation, and high-quality multimodal imaging. Hereafter, our own technical solution will be presented as a case.

[Screening for cerebral arteriovenous malformations in patients with hereditary haemorrhagic telangiectasia].

Patients with hereditary haemorrhagic telangiectasia (HHT) are known to suffer from cerebral arteriovenous malformations (CAVMs). In this review, we explore existing literature for bleeding risk, interventional therapy and neuroradiological features in HHT-related CAVMs. Studies estimate the annual intracerebral haemorrhage rate of CAVMs in HHT patients to be 0.667-1.014%. The clinician must balance bleeding risk and the non-negligible procedural risks of interventional therapy. We recommend, in agreement with European guidelines, that screening of asymptomatic HHT patients should only be carried out after careful information.

Depression severity is correlated to the integrity of white matter fiber tracts in late-onset major depression.

Cerebral white matter lesions (WMLs) are believed to play an important role in a subset of major depression (MD). We aimed to describe the impact of WMLs on white matter pathways in MD using diffusion tensor imaging (DTI) and magnetization transfer imaging. As a novel approach, we used DTI tractography to assess pathways intersected by WMLs. We examined 22 patients with late-onset MD and 22 age- and gender-matched controls. Parametric maps of fractional anisotropy (FA), apparent diffusion coefficient (ADC), and magnetization transfer ratio (MTR) were obtained to describe tissue integrity. The association between depression severity and the tract-specific localization of WMLs was analyzed on a voxel-by-voxel basis. We showed a significant positive association between depression severity and fiber tracts intersected by WMLs in the left superior longitudinal fasciculus and the right uncinate fasciculus. In both groups, WMLs had significantly lower FA and MTR, and higher ADC than both the tracts they intersected and the normal-appearing white matter (NAWM). In turn, the tracts intersected by WMLs had significantly lower FA and higher ADC than the NAWM. In conclusion, depression severity correlates with the tract-specific localization of WMLs. WMLs have a pronounced effect on white matter integrity in the pathways they intersect.

Neuropsychological Status and Structural Brain Imaging in Adults With Simple Congenital Heart Defects Closed in Childhood.

Background Neurodevelopmental impairments are common in survivors of complex congenital heart defects (CHD). We report neuropsychological and brain imaging assessments in adults operated for isolated septal defects. Methods and Results Patients (mean age 25.6 yrs) who underwent childhood surgery for isolated atrial septal defect (n=34) or ventricular septal defect (n=32), and healthy matched peers (n=40), underwent a standard battery of neuropsychological tests and a 3.0T brain magnetic resonance imaging scan. Patient intelligence was affected with lower scores on Full-Scale intelligence quotient (P<0.001), Verbal Comprehension (P<0.001), Perceptual Reasoning (P=0.007), and Working Memory (P<0.001) compared with controls. Also, the CHD group had poorer visuospatial abilities (Immediate Recall, P=0.033; Delayed Recall, P=0.018), verbal memory (Trial 1, P=0.015; Total Learning, P<0.001; Delayed Recall, P=0.007), executive function (Executive Composite Score, P<0.001), and social recognition (Reading the Mind in the Eyes Test, P=0.002) compared with controls. Self-reported levels of executive dysfunction, attention deficits and hyperactivity behavior, and social cognition dysfunction were higher in the CHD group compared with population means and controls. We found similar global and regional morphometric brain volumes and a similar frequency of brain magnetic resonance imaging abnormalities in the 2 groups. The CHD group had a high occurrence of psychiatric disease and a larger need for special teaching during school age. Conclusions Children operated for simple CHD demonstrate poorer neurodevelopmental outcomes in adulthood when compared with healthy controls and expected population means. REGISTRATION URL: https://www.clini​caltr​ials.gov. Unique identifier: NCT03871881.

Endovascular Treatment of Basilar Artery Thrombosis Secondary to Bilateral Vertebral Artery Dissection with Symptom Onset Following Cervical Spine Manipulation Therapy.

BACKGROUND: Vertebral artery (VA) dissection (VAD) has been described following neck injury and can be associated with stroke, but the causal association with cervical spine manipulation therapy (cSMT) is controversial. The standard treatment for VAD is antithrombotic medical therapy. To highlight the considerations of an endovascular approach to VAD, we present a critical case of bilateral VAD causing embolic occlusion of the basilar artery (BA) in a patient with symptom debut following cSMT. CASE REPORT: A 37-year-old woman presented with acute onset of neurological symptoms immediately following cSMT in a chiropractic facility. Acute magnetic resonance imaging (MRI) showed ischemic lesions in the right cerebellar hemisphere and occlusion of the cranial part of the BA. Angiography depicted bilateral VAD. Symptoms remitted after endovascular therapy, which included dilatation of the left VA and extraction of thrombus from the BA. After 6 months, the patient had minor sensory and cognitive deficits. CONCLUSIONS: In severe cases, VAD may be complicated by BA thrombosis, and this case highlights the importance of a fast diagnostic approach and advanced intravascular procedure to obtain good long-term neurological outcome. Furthermore, this case underlines the need to suspect VAD in patients presenting with neurological symptoms following cSMT.