Search

Abstract Background The harlequin syndrome is a rare disorder of the autonomic nervous system characterized by unilateral diminished flushing and sweating of the face following exposure to heat or physical activity. It results from sympathetic dysfunction and most commonly occurs idiopathically. A secondary development due to an underlying pathology (e.g., carotid artery dissection, tumors) must be excluded at first appearance. There is evidence that the cranial autonomic system is involved in the pathophysiology of trigeminal autonomic headaches like hemicrania continua. Therefore, an overlap in the pathophysiology of harlequin syndrome and trigeminal autonomic headache disorders seems plausible. However, the association of a harlequin syndrome with hemicrania continua was never reported. Case presentation This work describes the case of a 42‐year‐old female patient presenting to our headache unit. The patient reported persisting unilateral headache of the right side of dragging or squeezing character accompanied by trigeminal autonomic symptoms, including lacrimation, nasal congestion, conjunctival injection and Horner’s syndrome, and was responsive to treatment with 75mg/d indomethacin. Five months after the initial consultation, the patient noted that the upper right quadrant of her face was pale after jogging. A harlequin syndrome was diagnosed. Further, she developed a short-lasting, bilateral headache of pulsatile character during strenuous exercise consistent with exertional headache. Comprehensive diagnostic evaluations, encompassing cranial and cervical MRI scans, laboratory tests, and biopsies, culminated in the diagnosis of Sjögren’s syndrome. This finding suggests that the trigemino-autonomic dysfunction may either be idiopathic or a direct manifestation of Sjögren’s syndrome. Conclusions This report documents the case of a rare combination of a headache resembling probable hemicrania continua and the harlequin syndrome (and even exertional headache). It illustrates the underlying anatomy of the autonomic nervous system in a clinical context and emphasizes the hypothesis of a pathophysiological link between abnormal sympathetic activity and trigeminal autonomic headaches.

Abstract Large-scale imaging of brain activity with high spatio-temporal resolution is crucial for advancing our understanding of brain function. The existing neuroimaging techniques are largely limited by restricted field of view, slow imaging speed, or otherwise do not have the adequate spatial resolution to capture brain activities on a capillary and cellular level. To address these limitations, we introduce fluorescence localization microscopy aided with sparsely-labeled red blood cells for cortex-wide morphological and functional cerebral angiography with 4.9 µm spatial resolution and 1 s temporal resolution. When combined with fluorescence calcium imaging, the proposed method enables extended recordings of stimulus-evoked neuro-vascular changes in the murine brain while providing simultaneous multiparametric readings of intracellular neuronal activity, blood flow velocity/direction/volume, and vessel diameter. Owing to its simplicity and versatility, the proposed approach will become an invaluable tool for deciphering the regulation of cortical microcirculation and neurovascular coupling in health and disease.

Background Accumulating evidence suggests that cardiac findings after stroke are an important, yet understudied, manifestation of brain–heart interactions. Our aim was to investigate and compare cardiac findings after different cerebrovascular events (acute ischemic stroke, transient ischemic attack, and hemorrhagic stroke). Methods and Results There were 7113 patients screened who were treated between December 2013 and December 2020 at the University Hospital Zurich for ischemic stroke, transient ischemic attack, and hemorrhagic stroke. Seven hundred twenty‐one patients without evidence of previous cardiac disease or presumed cardioembolic origin of their cerebrovascular disease and with at least 1 cardiac checkup were included. Clinical reports from the year following disease onset were screened for new cardiac findings, which were categorized as arrhythmia/electrocardiographic changes, myocardial alterations, valvular abnormalities, and coronary perfusion insufficiency. Differences in proportions of findings among groups were analyzed using the Pearson χ2 test or Fisher exact test. ECG changes were observed in 81.7% (n=474) of patients with ischemic stroke, 71.4% (n=70) of patients with transient ischemic attack, and 55.8% (n=24) of patients with hemorrhagic stroke (P

Introduction The management of acute exacerbations of trigeminal neuralgia remains a major clinical challenge due to the limited availability of clinical evidence. This retrospective case series aims to evaluate the effectiveness and safety of intravenous phenytoin in the treatment of these exacerbations. Methods We retrospectively analyzed the outcome of patients treated with intravenous phenytoin for acute exacerbations of trigeminal neuralgia at the University Hospital Zurich between January 2016 and December 2023. Statistical analyses were performed to assess the associations of patient and disease characteristics with phenytoin response. Results In our sample of 45 cases, treatment with phenytoin resulted in a significant or complete relief in 30 cases (66.7%), while 11 (24.4%) experienced slight relief and 4 (8.9%) none. Patient or disease characteristics were not associated with treatment response. Side effects were rare, with skin itching occurring in only one case. Conclusion This retrospective case series demonstrates, that phenytoin is a safe and effective treatment for acute exacerbations of trigeminal neuralgia. However, larger prospective studies are needed.

Temporary, sudden, shooting and recurrent unilateral facial pain in the supply area of one or more trigeminal nerve branches characterises trigeminal neuralgia. Innocuous stimuli trigger the pain, e.g. chewing, speaking or brushing teeth. In some patients, paroxysms superimpose on continuous pain. In aetiological terms, idiopathic, classic (due to neurovascular compression) and secondary trigeminal neuralgia (e.g. due to multiple sclerosis, brainstem ischaemia and space-occupying lesions) are defined. Many drugs may be efficacious, with carbamazepine being first-choice therapy. However, non-pharmacological and invasive procedures may also help. To reach the correct diagnosis and determine the best therapeutic measures, adequate pain characterisation and interdisciplinary collaboration are essential. We hereby present our experience of an interdisciplinary approach for the diagnosis and treatment of trigeminal neuralgia.

Revascularization surgery for the symptomatic hemisphere with hemodynamic impairment is effective for Moyamoya vasculopathy patients. However, careful patient selection is crucial and ideally supported by advanced quantitative hemodynamic imaging. Recently, blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR) and quantitative magnetic resonance angiography with non-invasive optimal vessel analysis (qMRA-NOVA) have gained prominence in assessing these patients. This study aims to present the results of BOLD-CVR and qMRA-NOVA imaging along with the changes in cerebral hemodynamics and flow status following flow augmentation with superficial temporal artery–middle cerebral artery (STA-MCA) bypass in our Moyamoya vasculopathy patient cohort. Symptomatic patients with Moyamoya vasculopathy treated at the Clinical Neuroscience Center of the University Hospital Zurich who underwent hemodynamic and flow imaging (BOLD-CVR and qMRA-NOVA) before and after bypass were included in the analysis. Reduced hemispheric volume flow rates, as well as impaired BOLD-CVR, were measured in all 12 patients with Moyamoya vasculopathy before STA-MCA bypass surgery. Following the surgical procedure, post-operative BOLD-CVR demonstrated a non-significant increase in BOLD-CVR values within the revascularized, symptomatic middle cerebral artery territory and cerebral hemisphere. The results of the statistical tests should be viewed as indicative due to the small sample size. Additionally, post-operative qMRA-NOVA revealed a significant improvement in the hemispheric volume flow rate of the affected hemisphere due to the additional bypass flow rate. Our findings affirm the presence of hemodynamic and flow impairments in the symptomatic hemisphere of the Moyamoya vasculopathy patients. Bypass surgery proves effective in improving both BOLD-CVR impairment and the hemispheric volume flow rate in our patient cohort.

BackgroundThis study aimed to assess if there are sex differences in the functional outcome of intravenous thrombolysis (IVT) among patients with lacunar stroke (LS).MethodsConsecutive patients admitted from 1 January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry presenting with LS and treated with IVT were included. The study population was then divided into two groups based on patient sex, and a multivariable ordinal logistic regression analysis was performed to uncover sex differences in the modified Rankin Scale (mRS) score at 90 days after stroke.ResultsA total of 413 patients with LS were treated with IVT: 177 (42.9%) women and 236 (57.1%) men. Women were older than men (median age 74 years, 25th–75th percentiles 67–84 years versus 70 years, 25th–75th percentiles 60–80 years, value of p 0.001) and, after adjustment for meaningful variables, showed more frequently increased odds of a higher mRS score at 90 days after stroke (adjusted odds ratio 1.49, 95% confidence interval 1.01–2.19, value of p 0.044).ConclusionThis study showed that female sex increased the odds of a worse functional response to IVT in patients with LS. Future studies should further elucidate the mechanisms underlying such sex differences.

Abstract The intricate and delicate anatomy of the brain poses significant challenges for the treatment of cerebrovascular and neurodegenerative diseases. Thus, precise local drug delivery in hard-to-reach brain regions remains an urgent medical need. Microrobots offer potential solutions; however, their functionality in the brain remains restricted by limited imaging capabilities and complications within blood vessels, such as high blood flows, osmotic pressures, and cellular responses. Here, we introduce ultrasound-activated microrobots for in vivo navigation in brain vasculature. Our microrobots consist of lipid-shelled microbubbles that autonomously aggregate and propel under ultrasound irradiation. We investigate their capacities in vitro within microfluidic-based vasculatures and in vivo within vessels of a living mouse brain. These microrobots self-assemble and execute upstream motion in brain vasculature, achieving velocities up to 1.5 µm/s and moving against blood flows of ~10 mm/s. This work represents a substantial advance towards the therapeutic application of microrobots within the complex brain vasculature.

Dynamic perviousness is a novel imaging biomarker, with clot density measurements at multiple timepoints to allow longer contrast to thrombus interaction. We investigated the correlations between dynamic perviousness and clot composition in the setting of acute ischemic stroke. Thirty-nine patients with large vessel occlusion (LVO) undergoing mechanical thrombectomy (MT) were analyzed. Patients received a three-phase CT imaging pre-thrombectomy and histopathological analysis of retrieved clots. Clot densities for every phase and change in densities between phases were calculated, leading to four patterns of dynamic perviousness: no contrast uptake, early contrast uptake with and without washout and late uptake. Clots were categorized into three groups based on dominant histologic composition: red blood cell (RBC)-rich, fibrin/platelet-rich and mixed. Clot composition was correlated with dynamic perviousness using the Kruskal–Wallis test and Pearson’s correlation analysis. The dynamic perviousness categories showed a significant difference between fibrin-rich clots when compared to RBC-rich plus mixed groups. The uptake without washout category had significantly fewer fibrin clots compared to the uptake with washout (p = 0.036), and nearly significantly fewer fibrin clots when compared to the no uptake category (p = 0.057). Contrast uptake with different patterns of contrast washout showed significant differences of the likelihood for fibrin-rich clots.

Dissecting aneurysms in patients with spontaneous cervical artery dissections have, so far, been reported as “benign”, but more specific information is scarce. We aimed to elucidate (1) vascular risk factors, (2) local and ischemic symptoms, and (3) long-term prognosis compared to non-aneurysmal dissections. This case–control study included consecutive patients with spontaneous cervical artery dissection from three university hospitals in Switzerland and France, evaluated at baseline and at 3 months. In addition, further follow-ups were performed at the discretion of the treating physician. Dissecting aneurysms were diagnosed with duplex sonography, magnetic resonance angiography, and/or digital subtraction angiography. Of 1012 patients, 151 (14.9%) presented with 167 dissecting aneurysms at baseline (n = 103) or follow-up (n = 64). The median follow-up was 24.9 months (IQR: 6.8–60.8). Compared to patients without a dissecting aneurysm there were no significant differences in the vascular risk factors or local symptoms (91.4 vs. 89.8%). Ischemic strokes at baseline were less common (29.1% vs. 54.4%; OR: 0.41; 95% CI: 0.28–0.60) in patients with a dissecting aneurysm, even after correction for the degree of stenosis of the dissected arteries (OR: 0.53; 95% CI: 0.34–0.81). Patients with a dissecting aneurysm more often had a favorable clinical outcome (modified Rankin Scale Score of 0–1) at 3 months (80.6% vs. 54.5%). There was no significant difference in recurrent cerebrovascular events at 3 months or overall. The lower rate of ischemic strokes at baseline may reflect a different pathogenic mechanism, such as a smaller initial tear in the vessel wall or an increased vessel caliber from an early or primary intramural hematoma with a different shape.

Abstract Super-resolution optoacoustic imaging of microvascular structures deep in mammalian tissues has so far been impeded by strong absorption from densely-packed red blood cells. Here we devised 5 µm biocompatible dichloromethane-based microdroplets exhibiting several orders of magnitude higher optical absorption than red blood cells at near-infrared wavelengths, thus enabling single-particle detection in vivo. We demonstrate non-invasive three-dimensional microangiography of the mouse brain beyond the acoustic diffraction limit (

Background and Purpose This study aimed to investigate the effect of endovascular treatment (EVT, with or without intravenous thrombolysis [IVT]) versus IVT alone on outcomes in patients with acute ischemic stroke (AIS) and intracranial large vessel occlusion (LVO) attributable to cervical artery dissection (CeAD). Methods This multinational cohort study was conducted based on prospectively collected data from the EVA-TRISP (EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients) collaboration. Consecutive patients (2015–2019) with AIS-LVO attributable to CeAD treated with EVT and/or IVT were included. Primary outcome measures were (1) favorable 3-month outcome (modified Rankin Scale score 0–2) and (2) complete recanalization (thrombolysis in cerebral infarction scale 2b/3). Odds ratios with 95% confidence intervals (OR [95% CI]) from logistic regression models were calculated (unadjusted, adjusted). Secondary analyses were performed in the patients with LVO in the anterior circulation (LVOant) including propensity score matching. Results Among 290 patients, 222 (76.6%) had EVT and 68 (23.4%) IVT alone. EVT-treated patients had more severe strokes (National Institutes of Health Stroke Scale score, median [interquartile range]: 14 [10–19] vs. 4 [2–7], P

Leptomeningeal collaterals (LMCs) connect the main cerebral arteries and provide alternative pathways for blood flow during ischaemic stroke. This is beneficial for reducing infarct size and reperfusion success after treatment. However, a better understanding of how LMCs affect blood flow distribution is indispensable to improve therapeutic strategies. Here, we present a novel in silico approach that incorporates case-specific in vivo data into a computational model to simulate blood flow in large semi-realistic microvascular networks from two different mouse strains, characterised by having many and almost no LMCs between middle and anterior cerebral artery (MCA, ACA) territories. This framework is unique because our simulations are directly aligned with in vivo data. Moreover, it allows us to analyse perfusion characteristics quantitatively across all vessel types and for networks with no, few and many LMCs. We show that the occlusion of the MCA directly caused a redistribution of blood that was characterised by increased flow in LMCs. Interestingly, the improved perfusion of MCA-sided microvessels after dilating LMCs came at the cost of a reduced blood supply in other brain areas. This effect was enhanced in regions close to the watershed line and when the number of LMCs was increased. Additional dilations of surface and penetrating arteries after stroke improved perfusion across the entire vasculature and partially recovered flow in the obstructed region, especially in networks with many LMCs, which further underlines the role of LMCs during stroke.

Abstract It remains controversial which characteristics may predict occult cancer in stroke patients. Characteristics of patients with ischemic stroke registered in the Zurich Swiss Stroke Registry (2014 to 2016) were tested for associations with cancer diagnosis after stroke with consideration of death as competing risk for cancer diagnosis. Among 1157 patients, 34 (3%) and 55 patients (5%) were diagnosed with cancer within 1 and 3 years after stroke. Levels of white blood cells (WBC) > 9,600/µl (subdistribution hazard ratio (SHR) 3.68, p = 0.014), platelets > 400,000/µl (SHR 7.71, p = 0.001), and d-dimers ≥ 3 mg/l (SHR 3.67, p = 0.007) were independently associated with cancer diagnosis within 1 year after stroke. Occurrence of ischemic lesions in ≥ 2 vascular territories not attributed to cardioembolic etiology was associated with cancer diagnosed within 1 year after stroke in univariable analysis (SHR 3.69, p = 0.001). The area under the curve of a score from these parameters (score sum 0–4) was 0.73. A score of ≥ 2 had a sensitivity of 43% and specificity of 92% for prediction of cancer diagnosis within 1 year after stroke. We suggest further validation of a score of WBC, platelets, d-dimers and multiple ischemic lesions without cardioembolic stroke etiology for prediction of cancer diagnosis after stroke.

Many patients with cluster headaches report that their relatives do not understand what they are going through. This qualitative study aimed to collect patients’ recommendations and wishes on how others should respond to those suffering from cluster headaches. We recruited 22 patients with episodic or chronic cluster headaches for this cross-sectional study. They responded to seven questions that assessed the disease’s impact on their relationships with relatives and their wishes for others’ behaviour towards them. Seven recommendations for relatives emerged: (i) withdraw during attacks, (ii) respect post-ictal exhaustion, (iii) do not insist on discussing the disorder, (iv) help the patient to lead a “normal” life, (v) support preserving social contacts, (vi) show being aware of the disease severity, and (vii) expect the disease to take up space in patients’ lives and minds. Two recommendations for the interictal period indicate avoidance, which is considered a negative coping strategy. Conversely, the suggestion to support preserving social contacts might mean confronting the disease, which is likely associated with more favourable outcomes. Still, adhering to all patients’ requests might increase suffering instead of reducing it. Thus, further research is needed to develop strategies suited to improve well-being.

Recurrent stroke is a dreaded complication of symptomatic internal carotid artery occlusion (ICAO). Transcranial Duplex (TCD)-derived increased flow velocity in the ipsilateral posterior cerebral artery (PCA)-P2 segment indicates activated leptomeningeal collateral recruitment and hemodynamic impairment. Leptomeningeal collaterals are pial vascular connections between the anterior and posterior vascular territories. These secondary collateral routes are activated when primary collaterals via the Circle of Willis are insufficient. Our goal was to test the TCD parameter PCA-P2 flow for prediction of ipsilateral ischemia recurrence. We retrospectively analyzed clinical and ultrasound parameters in patients with ICAO. Together with clinical variables, we tested systolic PCA-P2 flow velocity as predictor of a recurrent ischemic event using logistic regression models. Of 111 patients, 13 showed a recurrent ischemic event within the same vascular territory. Increased flow in the ipsilateral PCA-P2 on transcranial ultrasound (median and interquartile range [IQR]: 60 cm/s [IQR 26] vs. 86 cm/s [IQR 41], p =

A 3D wide-field fluorescence microscopy method is introduced based on optical astigmatism combined with fluorescence source localization. It enables transcranial cortical microcirculation mapping in murine brain with high spatiotemporal resolution.

BackgroundAutoregulation of the cerebral vasculature keeps brain perfusion stable over a range of systemic mean arterial pressures to ensure brain functioning, e.g., in different body positions. Verticalization, i.e., transfer from lying (0°) to upright (70°), which causes systemic blood pressure drop, would otherwise dramatically lower cerebral perfusion pressure inducing fainting. Understanding cerebral autoregulation is therefore a prerequisite to safe mobilization of patients in therapy.AimWe measured the impact of verticalization on cerebral blood flow velocity (CBFV) and systemic blood pressure (BP), heart rate (HR) and oxygen saturation in healthy individuals.MethodsWe measured CBFV in the middle cerebral artery (MCA) of the dominant hemisphere in 20 subjects using continuous transcranial doppler ultrasound (TCD). Subjects were verticalized at 0°, −5°, 15°, 30°, 45° and 70° for 3–5 min each, using a standardized Sara Combilizer chair. In addition, blood pressure, heart rate and oxygen saturation were continuously monitored.ResultsWe show that CBFV progressively decreases in the MCA with increasing degrees of verticalization. Systolic and diastolic BP, as well as HR, show a compensatory increase during verticalization.ConclusionIn healthy adults CBFV changes rapidly with changing levels of verticalization. The changes in the circulatory parameters are similar to results regarding classic orthostasis.RegistrationClinicalTrials.gov, identifier: NCT04573114.

The brain and its health are essential for our (physical mental, social, and spiritual) wellbeing, for being able to realize our potential as individuals, and also for a fair, well-functioning, and productive society. However, today the world is facing a healthcare crisis related to the very high (and increasing) burden of brain disorders. As a response to this crisis, the “Swiss Brain Health Plan” (SBHP) was conceptualized in the context of other initiatives launched to value, promote, and protect brain health over the entire life course. In the first section of this position paper, the following fundamental considerations of the SBHP are discussed: (1) the high (and increasing) burden of brain disorders in terms of prevalence (>50% of the population suffers from a brain disorder), disability, mortality, and costs; (2) the prevention of brain disorders; (3) the operational definition of brain health; (4) determinants of brain health; (5) international initiatives to promote brain (including mental) health including the World Health Organization (WHO) intersectorial global action plan on epilepsy and other neurological disorders (NDs) (IGAP) and the WHO comprehensive mental health action plan. In the second section of the paper, the five strategic objectives of the SBHP, which has the vision of promoting brain health for all across the entire life course, are presented: (1) to raise awareness; (2) strengthen cross-disciplinary and interprofessional training/educational programs for healthcare professionals; (3) foster research on brain health determinants and individualized prevention of brain disorders; (4) prioritize a holistic (non-disease-specific), integrated, person-centered public health approach to promote brain health and prevent brain disorders through collaborations across scientific, health care, commercial, societal and governmental stakeholders and insurance providers; (5) support, empower, and engage patients, caregivers, and patient organizations, and reduce the stigma and discrimination related to brain disorders. In the third section of the paper, the first (2024) steps in the implementation of the SHBP, which will be officially launched in Zurich on 22 November 2023, are presented: (1) a definition of the overall organization, governance, specific targets, and action areas of the SBHP; (2) the patronage and/or co-organization of events on such specific topics as brain research (Lausanne), dementia (Geneva), stroke (Basel), neurohumanities (Bellinzona), sleep (Lugano), and psychiatry (Zurich); (3) the conduction of a new study on the global burden of brain disorders in Switzerland; (4) the launching of an international Certificate of Advanced Studies (CAS) on Brain Health at the University of Bern. In the fourth section of the paper, there is a concise executive summary of the SBHP.

Background and Purpose Knowledge about different etiologies of non-traumatic intracerebral hemorrhage (ICH) and their outcomes is scarce. Methods We assessed prevalence of pre-specified ICH etiologies and their association with outcomes in consecutive ICH patients enrolled in the prospective Swiss Stroke Registry (2014 to 2019). Results We included 2,650 patients (mean±standard deviation age 72±14 years, 46.5% female, median National Institutes of Health Stroke Scale 8 [interquartile range, 3 to 15]). Etiology was as follows: hypertension, 1,238 (46.7%); unknown, 566 (21.4%); antithrombotic therapy, 227 (8.6%); cerebral amyloid angiopathy (CAA), 217 (8.2%); macrovascular cause, 128 (4.8%); other determined etiology, 274 patients (10.3%). At 3 months, 880 patients (33.2%) were functionally independent and 664 had died (25.1%). ICH due to hypertension had a higher odds of functional independence (adjusted odds ratio [aOR], 1.33; 95% confidence interval [CI], 1.00 to 1.77; P=0.05) and lower mortality (aOR, 0.64; 95% CI, 0.47 to 0.86; P=0.003). ICH due to antithrombotic therapy had higher mortality (aOR, 1.62; 95% CI, 1.01 to 2.61; P=0.045). Within 3 months, 4.2% of patients had cerebrovascular events. The rate of ischemic stroke was higher than that of recurrent ICH in all etiologies but CAA and unknown etiology. CAA had high odds of recurrent ICH (aOR, 3.38; 95% CI, 1.48 to 7.69; P=0.004) while the odds was lower in ICH due to hypertension (aOR, 0.42; 95% CI, 0.19 to 0.93; P=0.031). Conclusions Although hypertension is the leading etiology of ICH, other etiologies are frequent. One-third of ICH patients are functionally independent at 3 months. Except for patients with presumed CAA, the risk of ischemic stroke within 3 months of ICH was higher than the risk of recurrent hemorrhage.

To improve risk stratification in extracranial internal carotid artery disease (CAD), patients who would benefit maximally from revascularization must be identified. In cardiology, the fractional flow reserve (FFR) has become a reference standard for evaluating the functional severity of coronary artery stenosis, and noninvasive surrogates thereof relying on computational fluid dynamics (CFD) have been developed. Here, we present a CFD-based workflow using digital twins of patients’ carotid bifurcations derived from computed tomography angiography for the noninvasive functional assessment of CAD. We reconstructed patient-specific digital twins of 37 carotid bifurcations. We implemented a CFD model using common carotid artery peak systolic velocity (PSV) acquired with Doppler ultrasound (DUS) as inlet boundary condition and a two-element Windkessel model as oulet boundary condition. The agreement between CFD and DUS on the PSV in the internal carotid artery (ICA) was then compared. The relative error for the agreement between DUS and CFD was 9% ± 20% and the intraclass correlation coefficient was 0.88. Furthermore, hyperemic simulations in a physiological range were feasible and unmasked markedly different pressure drops along two ICA stenoses with similar degree of narrowing under comparable ICA blood flow. Hereby, we lay the foundation for prospective studies on noninvasive CFD-based derivation of metrics similar to the FFR for the assessment of CAD.

Abstract Quantitative susceptibility mapping (QSM) is a novel processing method for gradient-echo magnetic resonance imaging (MRI). Higher magnetic susceptibility in cortical veins have been observed on susceptibility maps in the ischemic hemisphere of stroke patients, indicating an increased oxygen extraction fraction (OEF). Our goal was to investigate susceptibility in veins of stroke patients after successful recanalization in order to analyze the value of QSM in predicting tissue prognosis and clinical outcome. We analyzed MR images of 23 patients with stroke due to unilateral middle cerebral artery (MCA)-M1/M2 occlusion acquired 24–72 h after successful thrombectomy. The susceptibilities of veins were obtained from QSM and compared between the stroke territory, the ipsilateral non-ischemic MCA territory and the contralateral MCA territory. As outcome variables, early infarct size and functional disability (modified Rankin Scale, mRS) after 3–5 months was used. The median susceptibility value of cortical veins in the ischemic core was 41% lower compared to the ipsilateral non-ischemic MCA territory and 38% lower than on the contralateral MCA territory. Strikingly, in none of the patients prominent vessels with high susceptibility signal were found after recanalization. Venous susceptibility values within the infarct did not correlate with infarct volume or functional disability after 3–5 months. Low venous susceptibility within the infarct core after successful recanalization of the occluded vessel likely indicates poor oxygen extraction arising from tissue damage. We did not identify peri-infarct tissue with increased susceptibility values as potential surrogate of former penumbral areas. We found no correlation of QSM parameters with infarct size or outcome.

Background: Diagnosing headache disorders comprises the collection and interpretation of information. This study estimates agreement and bias in the latter. Methods: Physicians and medical students diagnosed eight patients’ headaches using the International Classification of Headache Disorders. We calculated Cohen’s Kappa for all participants and subgroups (board-certified neurologists, physicians working in a neurology department). Moreover, we asked how sure they felt about their diagnoses. Finally, participants estimated the number of different headache diagnoses a patient receives when consulting many physicians for the same headache and indicated the highest acceptable number. Results: The data of 63 participants entered the analysis, of whom 18 were neurologists (18/63, 28.6%), and 41 were currently working at a neurology clinic (41/63, 66.7%). Cohen’s Kappa decreased (0.706, 0.566, and 0.408) with increasing levels of the classification hierarchy. Interrater agreement was highest among neurologists. Physicians not working in a neurology clinic tended to diagnose secondary headaches more often were less confident about their diagnoses. Conclusions: Physicians with less experience in headache disorders struggle more to diagnose headaches than neurologists do; they suspect secondary headaches, disagree, and feel insecure more often. Thus, interpreting a headache history is prone to error and bias.

Unilateral head and neck pain is a hallmark of cervical artery dissection (CAD). While pain is conceived as an alarming sign for patients and often leads to discovery of the dissection, it is not known if persistence of pain is associated with the course of CAD. Potentially, pain could indicate persisting vessel pathology and thus guide treatment decisions aimed at reducing risk of ischemic stroke in CAD. We performed a retrospective analysis of data from patients with CAD treated at the University Hospital Zurich (USZ). Only patients with information about the presence of pain, independence after CAD according to the modified Rankin scale (mRS), and imaging-based information on vessel status were included. Patients were grouped according to presence/absence of head and/or neck pain on admission and at a three-month follow-up. We used descriptive statistics and logistic regression to reveal a potential association between pain on admission and pain at follow-up with status of the dissected vessel at follow-up (open vs. stenosed or occluded). We screened 139 patients with CAD between 2014 and 2019 and included 68. Fifty-nine patients (86.8%) had pain on admission, which was resolved in 46 (68%) at follow-up. Our post hoc analysis revealed that more patients with headache or neck pain on admission had a migraine diagnosis in medical history (n = 7 (10.4%) vs. n = 0 (0%), p = 0.029) and that NIHSS on admission was higher in patients with no pain at presentation (group B NIHSS = 3, IQR 8 vs. group A NIHSS = 2, IQR 5, group C NIHSS = 0, IQR 2, p = 0.041). There were no other differences between the three patient groups in the descriptive analysis. Logistic regression analysis for vessel status at follow-up did not show an association with pain on admission or at follow-up. In our cohort of patients with CAD, headache was a common initial clinical presentation, which rarely persisted for three months. Headache on admission or at follow-up did not predict persisting vessel pathology in patients with CAD.

Primary headaches are a common debilitating health condition. Proper diagnosis and treatment depend on patients’ communication. We wanted to explore differences in pain communication with a special interest in potential sex differences. Patients visiting our headache unit for the first time filled in two different questionnaires (one before entering the consultation and one directly after finishing the consultation), through which we captured patients’ descriptions of their pain, its potential impact on daily lives, the well-being of our patients and the satisfaction with our consultation. We included a total of 35 patients (22 female, 13 male). Women reported experiencing a greater loss of socially active days during the last 3 months because of headaches compared to men. Furthermore, women were more satisfied with our consultation. In addition, we revealed migraineurs characterize their pain differently than stated in the International Classification of Headache Disorders (ICHD-3) criteria. The adjective “pressing” (drückend) was used significantly more often by migraineurs compared to patients with tension-type headaches. Nevertheless, in the physicians’ written report, the characterization more often contained the ICHD-3 corresponding adjective “pulsating” (pulsierend). Since the typification of headaches and subsequent therapy depends predominantly on the patients’ communication, consideration of the individual pain description and further research on headache characterization are indispensable.

Patients with cluster headache often report a long diagnostic delay. This study creates and validates a screening test that could help speed up the diagnostic process. We invited patients to enrol in this diagnostic case–control study if a trigeminal autonomic headache had been suspected or confirmed. Patients in whom the diagnosis of a cluster headache was not made were controls. First, all participants answered 22 diagnostic questions with “yes” or “no”. Next, we eliminated questions that did not distinguish well between the groups. Then, the variables entered a regression model with the headache diagnosis as the dependent variable. Finally, we combined the remaining variables into a diagnostic scale and tested its accuracy. Seventy-four patients participated, 45 of whom suffered from a cluster headache. The analyses identified five questions distinguishing cluster headache patients and controls. These addressed smoking, being awakened by the pain, restlessness during the attack, unilateral tearing, and duration of the attack (hence, the “SMARTED” scale). The area under the ROC curve was 0.938; sensitivity and specificity, the positive and negative predictive values were 98%, 65%, 81% and 94%, respectively. The SMARTED scale validly and accurately screens for cluster headache in patients suspected of a trigeminal autonomic headache.

Purpose The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry.Participants All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS).Findings to date Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups.Future plans This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.

Background Comprehensive hemodynamic impairment mapping using blood oxygenation‐level dependent (BOLD) cerebrovascular reactivity (CVR) can be used to identify hemodynamically relevant symptomatic unilateral carotid artery disease. Methods and Results This prospective cohort study was conducted between February 2015 and July 2020 at the Clinical Neuroscience Center of the University Hospital Zurich, Zurich, Switzerland. One hundred two patients with newly diagnosed symptomatic unilateral internal carotid artery (ICA) occlusion or with 70% to 99% ICA stenosis were included. An age‐matched healthy cohort of 12 subjects underwent an identical BOLD functional magnetic resonance imaging examination. Using BOLD functional magnetic resonance imaging with a standardized CO2 stimulus, CVR impairment was evaluated. Moreover, embolic versus hemodynamic ischemic patterns were evaluated on diffusion‐weighted imaging. Sixty‐seven patients had unilateral ICA occlusion and 35 patients unilateral 70% to 99% ICA stenosis. Patients with ICA occlusion exhibited lower whole‐brain and ipsilateral hemisphere mean BOLD‐CVR values as compared with healthy subjects (0.12±0.08 versus 0.19±0.04, P=0.004 and 0.09±0.09 versus 0.18±0.04, P

Current treatment for acute ischemic stroke aims at recanalizing the occluded blood vessel to reperfuse ischemic brain tissue. Clot removal can be achieved pharmacologically with a thrombolytic drug, such as recombinant tissue plasminogen activator, or with mechanical thrombectomy. However, reopening the occluded vessel does not guarantee full tissue reperfusion, which has been referred to as reperfusion failure. When it occurs, reperfusion failure significantly attenuates the beneficial effect of recanalization therapy and severely affects functional recovery of stroke patients. The mechanisms of reperfusion failure are somewhat complex and not fully understood. Briefly, after stroke, capillaries show stalls, constriction and luminal narrowing, being crowded with neutrophils, and fibrin–platelet deposits. Furthermore, after recanalization in stroke patients, a primary clot can break, dislodge, and occlude distal arterial branches further downstream. In this review, we highlight a rodent model that allows studying the pathophysiological mechanisms underlying reperfusion failure after stroke. We also describe the vascular and intravascular changes involved in reperfusion, which may provide relevant therapeutic targets for improving treatment of stroke patients.

In acute ischemic stroke, intravenous thrombolysis (IVT) and acute endovascular therapy (EVT) have been shown to reduce long-term disability in randomized trials. International guidelines are partially not up to date and may not address situations for which there is limited scientific evidence. The goals of the present guidelines are to summarize the current scientific data for acute revascularization treatments to make sure that all Swiss Centers apply a similar, evidence, or consensus-based treatment standard. A multidisciplinary working group of the Swiss Stroke Society (SSS) searched and reviewed the literature on new randomized controlled trials (RCTs), large case series, meta-analyses, and other guidelines since the previous recommendations in 2009 to elaborate the consensus guidelines. The new RCTs have confirmed the effectiveness of IVT in various populations up to 4.5 h and proven the benefit of acute EVT up to approximately 8 h. For patients with unknown onset (including wake-up stroke), IVT and EVT can be effective up to 24 h after last proof of good health if patients are selected with advanced neuroimaging. Multiple case series and meta-analyses allow narrowing down the indications and relative and absolute contraindications to optimize the benefit–risk ratio of acute revascularization.

Abstract Many stroke survivors experience persisting episodic memory disturbances. Since hippocampal and para-hippocampal areas are usually spared from the infarcted area, alterations of memory processing networks remote from the ischemic brain region might be responsible for the observed clinical symptoms. To pinpoint changes in activity of hippocampal connections and their role in post-stroke cognitive impairment, we induced ischemic stroke by occlusion of the middle cerebral artery (MCAO) in adult rats and analyzed the functional and structural consequences using activity-dependent manganese (Mn2+) enhanced MRI (MEMRI) along with behavioral and histopathological analysis. MCAO caused stroke lesions of variable extent along with sensorimotor and cognitive deficits. Direct hippocampal injury occurred in some rats, but was no prerequisite for cognitive impairment. In healthy rats, injection of Mn2+ into the entorhinal cortex resulted in distribution of the tracer within the hippocampal subfields into the lateral septal nuclei. In MCAO rats, Mn2+ accumulated in the ipsilateral thalamus. Histopathological analysis revealed secondary thalamic degeneration 28 days after stroke. Our findings provide in vivo evidence that remote sensorimotor stroke modifies the activity of hippocampal-thalamic networks. In addition to potentially reversible alterations in signaling of these connections, structural damage of the thalamus likely reinforces dysfunction of hippocampal-thalamic circuitries.

Over the last decade, neuroimaging methods have been refined to improve clinical decisions regarding acute stroke treatment. Computed tomography and magnetic resonance imaging are routinely used to rule out intracerebral haemorrhage or other contraindications of thrombolysis, to detect stroke mimics and to estimate the time of stroke onset. With the availability of fast and advanced imaging methods, there is a growing interest in expanding their application for the prediction of success and risks of specific therapies. The mismatch concept, which has long been controversial, has now experienced a breakthrough due to further development and standardisation of imaging parameters, and a separation of different, clinically relevant mismatch patterns. In this review, we will highlight existing neuroimaging modalities for acute stroke. To interpret neuroimaging results, knowledge about the clinical situation is essential. Furthermore, the factors of time since stroke onset and collateral blood supply need to be incorporated into existing imaging-based therapeutic strategies.

The impact of excess body weight on prognosis after stroke is controversial. Many studies report higher survival rates in obese patients ("obesity paradox"). Recently, obesity has been linked to worse outcomes after intravenous (IV) thrombolysis, but the number and sample size of these studies were small. Here, we aimed to assess the relationship between body weight and stroke outcome after IV thrombolysis in a large cohort study.In a prospective observational multicenter study, we analyzed baseline and outcome data of 896 ischemic stroke patients who underwent IV thrombolysis. Patients were categorized according to body mass index (BMI) as underweight (35 kg/m2). Using uni- and multivariate modeling, we assessed the relationship of BMI with favorable outcome (defined as modified Rankin Scale 0 or 1) and mortality 3 months after stroke as well as the occurrence of symptomatic intracerebral hemorrhages (sICH). We also measured the incidence of patients that had an early neurological improvement of >40% on the National Institutes of Health Stroke Scale (NIHSS) after 24 hours.Among 896 patients, 321 were normal weight (35.8%), 22 underweight (2.5%), 378 overweight (42.2%), 123 obese (13.7%) and 52 severely obese (5.8%). Three-month mortality was comparable in obese vs. non-obese patients (8.1% vs. 8.3%) and did not differ significantly among different BMI groups. This was also true for favorable clinical outcome, risk of sICH and early neurological improvement on NIHSS at 24 hours. These results remained unchanged after adjusting for potential confounding factors in the multivariate analyses.BMI was not related to clinical outcomes in stroke patients treated with IVT. Our data suggest that the current weight-adapted dosage scheme of IV alteplase is appropriate for different body weight groups, and challenge the existence of the obesity paradox after stroke.

Inflammatory myopathies such as dermatomyositis and polymyositis are well-recognized paraneoplastic syndromes. Little is known, however, about necrotizing myopathies in association with cancer. We here describe a case of paraneoplastic necrotizing myopathy with a mild inflammatory infiltrate in a patient with adenocarcinoma. After the rapid development of a severe, disabling muscle weakness, the patient experienced near complete recovery within 4 months under oral prednisone treatment. In the context of the presented case, we will review current knowledge about paraneoplastic necrotizing myopathies.

Ischemic stroke is caused by a disruption in blood supply to a region of the brain. It induces dysfunction of brain cells and networks, resulting in sudden neurological deficits. The cause of stroke is vascular, but the consequences are neurological. Decades of research have focused on finding new strategies to reduce the neural damage after cerebral ischemia. However, despite the incredibly huge investment, all strategies targeting neuroprotection have failed to demonstrate clinical efficacy. Today, treatment for stroke consists of dealing with the cause, attempting to remove the occluding blood clot and recanalize the vessel. However, clinical evidence suggests that the beneficial effect of post-stroke recanalization may be hampered by the occurrence of microvascular reperfusion failure. In short: recanalization is not synonymous with reperfusion. Today, clinicians are confronted with several challenges in acute stroke therapy, even after successful recanalization: (1) induce reperfusion, (2) avoid hemorrhagic transformation (HT), and (3) avoid early or late vascular reocclusion. All these parameters impact the restoration of cerebral blood flow after stroke. Recent advances in understanding the molecular consequences of recanalization and reperfusion may lead to innovative therapeutic strategies for improving reperfusion after stroke. In this review, we will highlight the importance of restoring normal cerebral blood flow after stroke and outline molecular mechanisms involved in blood flow regulation.

In vivo monitoring of cells labeled with paramagnetic iron oxide particles by magnetic resonance imaging (MRI) is complicated by intrinsic contrast of blood vessels. Distinction between T 2 * effects caused by blood vessels from those caused by labeled cells was so far only possible after carefully following the location of hypointense regions through subsequent slices of T 2 *-weighted 3-D MRI datasets, a procedure that is time consuming and not always reliable in the case of smaller blood vessels. Here, we demonstrate that the modification of the inhalation gas mixture from the routinely used composition 35% O 2 and 65% N 2 O to a mixture containing 95% O 2 and 5% CO 2 results in a contrast suppression of most small blood vessels and reduces the intrinsic T 2 * effect of large vessels dramatically in an animal model. This change in protocol of physiological conditions was well tolerated by all studied animals, even over prolonged experimental times. The changed inhalation gas mixture thus provides a more reliable identification method for small clusters of iron oxide labeled cells in vivo.

Background We investigated outcomes in patients with intracerebral haemorrhage (ICH) according to prior anticoagulation treatment with Vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or no anticoagulation.Methods This is an individual patient data study combining two prospective national stroke registries from Switzerland and Norway (2013–2019). We included all consecutive patients with ICH from both registries. The main outcomes were favourable functional outcome (modified Rankin Scale 0–2) and mortality at 3 months.Results Among 11 349 patients with ICH (mean age 73.6 years; 47.6% women), 1491 (13.1%) were taking VKAs and 1205 (10.6%) DOACs (95.2% factor Xa inhibitors). The median percentage of patients on prior anticoagulation was 23.7 (IQR 22.6–25.1) with VKAs decreasing (from 18.3% to 7.6%) and DOACs increasing (from 3.0% to 18.0%) over time. Prior VKA therapy (n=209 (22.3%); adjusted ORs (aOR), 0.64; 95% CI, 0.49 to 0.84) and prior DOAC therapy (n=184 (25.7%); aOR, 0.64; 95% CI, 0.47 to 0.87) were independently associated with lower odds of favourable outcome compared with patients without anticoagulation (n=2037 (38.8%)). Prior VKA therapy (n=720 (49.4%); aOR, 1.71; 95% CI, 1.41 to 2.08) and prior DOAC therapy (n=460 (39.7%); aOR, 1.28; 95% CI, 1.02 to 1.60) were independently associated with higher odds of mortality compared with patients without anticoagulation (n=2512 (30.2%)).Conclusions The spectrum of anticoagulation-associated ICH changed over time. Compared with patients without prior anticoagulation, prior VKA treatment and prior DOAC treatment were independently associated with lower odds of favourable outcome and higher odds of mortality at 3 months. Specific reversal agents unavailable during the study period might improve outcomes of DOAC-associated ICH in the future.