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We have seen in many circumstances of cancer research and clinical practice that the process itself is more critical and valuable than the result. For better presenting the natural movements of studied subject as well as the processes of medical intervention in treating patient, we proudly launch Visualized Cancer Medicine as a peer-reviewed publication platform covering all relevant topics in which videos play a critical role for presenting the results or the procedures. We appreciate the constant supports from our rigorous authors, dedicating editorial staff members, creative informative technology engineers, and enthusiastic readers. We hope that our small step of establishing Visualized Cancer Medicine for better scientific presentation would foster giant leaps of our understanding on cancer, which would subsequently benefit human being in many ways.

Abstract Background MicroRNAs are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many cancers including hematological malignancies. However, the role of microRNAs in the pathogenesis of multiple myeloma (MM) is only poorly understood. We therefore used microarray analysis to elucidate the complete miRNome (miRBase version 13.0) of purified tumor (CD138+) cells from 33 patients with MM, 5 patients with monoclonal gammopathy of undetermined significance (MGUS) and 9 controls. Results Unsupervised cluster analysis revealed that MM and MGUS samples have a distinct microRNA expression profile from control CD138+ cells. The majority of microRNAs aberrantly expressed in MM (109/129) were up-regulated. A comparison of these microRNAs with those aberrantly expressed in other B-cell and T-cell malignancies revealed a surprising degree of similarity (~40%) suggesting the existence of a common lymphoma microRNA signature. We identified 39 microRNAs associated with the pre-malignant condition MGUS. Twenty-three (59%) of these were also aberrantly expressed in MM suggesting common microRNA expression events in MM progression. MM is characterized by multiple chromosomal abnormalities of varying prognostic significance. We identified specific microRNA signatures associated with the most common IgH translocations (t(4;14) and t(11;14)) and del(13q). Expression levels of these microRNAs were distinct between the genetic subtypes (by cluster analysis) and correctly predicted these abnormalities in > 85% of cases using the support vector machine algorithm. Additionally, we identified microRNAs associated with light chain only myeloma, as well as IgG and IgA-type MM. Finally, we identified 32 microRNAs associated with event-free survival (EFS) in MM, ten of which were significant by univariate (logrank) survival analysis. Conclusions In summary, this work has identified aberrantly expressed microRNAs associated with the diagnosis, pathogenesis and prognosis of MM, data which will prove an invaluable resource for understanding the role of microRNAs in this devastating disease. Reviewers This article was reviewed by Prof. Neil Smalheiser, Prof. Yuriy Gusev, and an unknown reviewer.

Aim: To investigate the prognostic implication (mortality at 3 months) of acute kidney injury (AKI) in acute ischemic stroke treated with mechanical thrombectomy (MT)., Material and Methods: A literature search was performed using PubMed/OVID/Cochran's CENTRAL database (time frame: inception to January 2023). Study characteristics, patient status, clinical outcomes, AKI incidence, and sample size were recorded. The exclusion criteria were non-English literature, no human subjects, and <10 patients as the sample size. Studies were assessed using the MINORS/GRADE system. Meta-analysis and meta-regression with a random-effects model were performed., Results: 3314 studies were retrieved. After applying the exclusion criteria, the final population included of 18/3314 studies (0.5%). Among them, only 6/18 (33.3%) studies reported results in two separate groups (AKI vs non-AKI), allowing for inference statistics for a total population of 3229 (538.6 ± 403.7). The I^2 was 34.6 and Q's Cochrane was 7.80. The pooled odds ratio (OR) for mortality at 3 months in patients with AKI was 5.8 (95% confidence interval [95% CI] 95% CI 3.62 to 9.52). Leave-one-out meta-analysis showed no significant sources of heterogeneity. In the meta-regression, diabetes prevalence was associated with a higher mortality rate (OR 1.14, 95% CI 1.03 to 1.28), and lower age and a small amount of contrast media were negatively correlated (0.91 [95% CI 0.83 to 0.99] and OR 0.97 [95% CI 0.94 to 1.00], respectively)., Conclusion: AKI was significantly associated with the mortality rate in MT-treated stroke patients (OR 5.8 [95% CI 3.62 to 9.36])., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: To investigate the optimum antiplatelet therapy regimen (APTR) for emergent carotid artery stenting following mechanical thrombectomy (MT) in stroke patients with tandem occlusion., Methods: A literature search was performed on Pubmed/OVID/Cochran's CENTRAL database for studies from 2015 to 2022. Patient characteristics, antiplatelet regimen type, mTICI, 90 days-mRS, acute in-stent thrombosis (AIST), mortality, intracranial hemorrhage (ICH), and sample size were recorded. Exclusion criteria were non-English literature, sample size < 5 patients, other anticoagulant/antiplatelet therapy, and 100 % stent insertion in one study arm. The studies were assessed using MINORS/GRADE. Meta-analysis and meta-regression with a random effects model were performed. The outcomes were: 90 days-mRS, death, AIST and ICH RESULTS: Five-hundred-twenty-four studies were retrieved. After applying the exclusion criteria, the final population included 19/534 studies (3.6 %) for 880 patients (46.3 per article). I^2 and Q's Cochrane were 86.4 % and 132.5 for mRS, 19.9 % and 17.5 for death, 0 % and 9.4 for acute in-stent thrombosis and 62.1 % and 39.7 for intra-cranial haemorrhages, respectively. Patients in the aspirin subgroup had a significantly lower rate of functional independence (mRS≤2) than those in the DAPT subgroup (47 % [CI95 % 42.0 %-52.0 %] vs. 61.9 % [CI95 % 50.8-72.9]; p=0.0007;OR 0.75[CI95 % 0.56-1.01], p=0.06). DAPT significantly decreased the death rate compared with aspirin (8.6 % [CI95 % 5.3 %-11.9 %] vs. 16.7 % [CI95 11.1 %-22.2 %]; p=0.0012). Anti-GPIIb/IIIa demonstrated a trend of increasing the probability of mortality versus DAPT (OR 1.88[CI95 % 0.93-3.86], p=0.08. No significant differences were observed between AIST and ICH in the treatment groups., Conclusion: DAPT may increases the chance of obtaining an mRS score ≤2 and reduces mortality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cerebellar mutism syndrome (CMS) is a frequent complication of surgical intervention on posterior fossa in children. It has been only occasionally reported in adults and its features have not been fully characterized. In children and in young adults, medulloblastoma is the main reason for neurosurgery. A single case of postsurgical CMS is presented in an adult patient with a cerebellar hemorrhage and a systematic review of the published individual cases of CMS in adults was done. Literature review of individual cases found 30 patients, 18/30 (60%) males, from 20 to 71 years at diagnosis. All but one case was post-surgical, but in one of the post-surgical cases iatrogenic basilar artery occlusion was proposed as cause for CMS. The causes were: primary tumors of the posterior fossa in 16/22 (72.7%) metastasis in 3/30 (10%), ischemia in 3/30 (10%) cerebellar hemorrhage in 3/30 (10%), and benign lesions in 2/30 (6.7%) patients. 8/30 patients (26.7%) were reported as having persistent or incomplete resolution of CMS within 12 months. CMS is a rare occurrence in adults and spontaneous cerebellar hemorrhage has been reported in 3/30 (10%) adult patients. The generally accepted hypothesis is that CMS results from bilateral damage to the dentate nucleus or the dentate-rubro-thalamic tract, leading to cerebro-cerebellar diaschisis. Several causes might contribute in adults. The prognosis of CMS is slightly worse in adults than in children, but two thirds of cases show a complete resolution within 6 months., (© 2024. Fondazione Società Italiana di Neurologia.)

Spontaneous convexity subarachnoid hemorrhage (cSAH) is a vascular disease different from aneurysmal SAH in neuroimaging pattern, causes, and prognosis. Several causes might be considered in individual patients, with a limited value of the patient's age for discriminating among these causes. Cerebral amyloid angiopathy (CAA) is the most prevalent cause in people > 60 years, but reversible cerebral vasoconstriction syndrome (RCVS) has to be considered in young people. CAA gained attention in the last years, but the most known manifestation of cSAH in this context is constituted by transient focal neurological episodes (TFNEs). CAA might have an inflammatory side (CAA-related inflammation), whose diagnosis is relevant due to the efficacy of immunosuppression in resolving essudation. Other causes are hemodynamic stenosis or occlusion in extracranial and intracranial arteries, infective endocarditis (with or without intracranial infectious aneurysms), primary central nervous system angiitis, cerebral venous thrombosis, and rarer diseases. The diagnostic work-up is fundamental for an etiological diagnosis and includes neuroimaging techniques, nuclear medicine techniques, and lumbar puncture. The correct diagnosis is the first step for choosing the most effective and appropriate treatment.

Argyria is the chronic accumulation of silver in biological tissues such as skin, liver, kidneys, lungs, peripheral nerves, and brain. The presence of an actual pathophysiological and clinical correlate related to silver encephalic and peripheral nerve deposition is still much debated. In this paper, we reviewed and described case reports regarding argyria associated with neuropsychiatric symptoms in order to explain the underlying mechanism of the disease. We conducted a narrative review by searching for case reports that described subjects with chronic silver accumulation and who had associated neurological or psychiatric symptoms. Moreover, we report a case of a 50-year-old man admitted to our hospital with a diagnosis of major depression who presented with worsening psychiatric symptoms after abuse of silver-containing nasal spray. We found 15 cases of patients with argyria and neuropsychiatric manifestations such as epilepsy, neurodegenerative syndromes, multiple sclerosis, peripheral neuropathy, and psychiatric disorders. The knowledge of possible pathogenetic mechanisms and recognition of clinical features of argyria can help clinicians prevent brain deposition and its complications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Antiphospholipid syndrome (APS) is an autoimmune prothrombotic condition characterized by venous thromboembolism, arterial thrombosis, and pregnancy morbidity. Among neurological manifestations, arterial thrombosis is only one of the possible associated clinical and neuroradiological features. The aim of this review is to address from a neurovascular point of view the multifaceted range of the arterial side of APS. A modern neurovascular approach was proposed, dividing the CNS involvement on the basis of the size of affected arteries, from large to small arteries, and corresponding clinical and neuroradiological issues. Both large-vessel and small-vessel involvement in APS were detailed, highlighting the limitations of the available literature in the attempt to derive some pathomechanisms. APS is a complex disease, and its neurological involvement appears multifaceted and not yet fully characterized, within and outside the diagnostic criteria. The involvement of intracranial large and small vessels appears poorly characterized, and the overlapping with the previously proposed inflammatory manifestations is consistent.

Background: Contrast media used in mechanical therapies for stroke and myocardial infarction represent a significant cause of acute kidney injury (AKI) in acute medical scenarios. Although the continuous saline infusion line (CSIL) is a standard procedure to prevent thrombus formation within the catheter during neurovascular interventions of mechanical thrombectomy (MT), it is not utilized in percutaneous coronary interventions (PCI)., Methods: A systematic review of the incidence of AKI after MT for stroke treatment was performed. These data were compared with those reported in the literature regarding the incidence of AKI after PCI for acute myocardial infarction. A random-effect model meta-regression was performed to explore the effects of CSIL on AKI incidence, using clinical details as covariates., Results: A total of 18 and 33 studies on MT and PCI were included, respectively, with 69,464 patients (30,138 [43.4%] for MT and 39,326 [56.6%] for PCI). The mean age was 63.6 years±5.8 with male 66.6%±12.8. Chronic kidney disease ranged 2.0-50.3%. Diabetes prevalence spanned 11.1% to 53.0%. Smoking status had a prevalence of 7.5-72.0%. Incidence of AKI proved highly variable (I 2 =98%, Cochrane's Q 2985), and appeared significantly lower in the MT subgroup than in the PCI subgroups (respectively 8.3% [95% confidence interval: 4.7-11.9%] vs. 14.7 [12.6-16.8%], P<0.05). Meta-regression showed that CSIL was significantly associated with a decreased incidence of AKI (OR=0.93 [1.001-1.16]; P=0.03)., Conclusions: Implementation of CSIL during endovascular procedures in acute settings was associated with a significant decrease in the risk of AKI, and its safety should be routinely considered in such interventions.

The full-scale Russian invasion of Ukraine has significantly impacted the country's healthcare system. Insufficient infrastructure, destruction of medical facilities, and barriers to prevention and treatment efforts hinder the provision of timely, high-quality care to our patients. We aim to describe the impact of the war on neurological care across Ukraine. In this article, leading national experts in stroke, epilepsy, multiple sclerosis, and movement disorders describe their personal experience and efforts in organizing and providing care since the war started in February 2022. A neurologist who cared for patients in Mariupol recounts the first weeks of the war when the city was under constant attacks. An international stroke expert describes the role of Task Force for Ukraine, a European Stroke Organization initiative to support the Ukrainian stroke community. We discuss a series of critical challenges facing Ukraine's neurologists, patients, and healthcare delivery system, including shortages of personnel and medical supplies, disrupted logistics, and lack of funding. In addition, we highlight various interventions and strategies aimed at counteracting these challenges, including international support, collaborations within Ukraine, and initiatives enhancing the resilience of the Ukrainian neurology community. As the war is ongoing, this article emphasizes the pressing need for continuous support and investment in the Ukrainian healthcare system to preserve guaranteed access to high-quality healthcare for the Ukrainian people during the war and in its aftermath. Insights from the essays can inform the development and implementation of effective strategies and interventions tailored to such extraordinary circumstances., Competing Interests: None declared., (Thieme. All rights reserved.)

Primary Angiitis of the Central Nervous System (PACNS) is a rare cerebrovascular disease involving the arteries of the leptomeninges, brain and spinal cord. Its diagnosis can be challenging, and the current diagnostic criteria show several limitations. Among the clinical and neuroimaging manifestations of PACNS, intracranial bleeding, particularly intracerebral hemorrhage (ICH), is poorly described in the available literature, and it is considered infrequent. This review aims to summarize the available data addressing this issue with a dedicated focus on the clinical, neuroradiological and neuropathological perspectives. Moreover, the limitations of the actual data and the unanswered questions about hemorrhagic PACNS are addressed from a double point of view (PACNS subtyping and ICH etiology). Fewer than 20% of patients diagnosed as PACNS had an ICH during the course of the disease, and in cases where ICH was reported, it usually did not occur at presentation. As trigger factors, both sympathomimetic drugs and illicit drugs have been proposed, under the hypothesis of an inflammatory response due to vasoconstriction in the distal cerebral arteries. Most neuroradiological descriptions documented a lobar location, and both the large-vessel PACNS (LV-PACNS) and small-vessel PACNS (SV-PACNS) subtypes might be the underlying associated phenotypes. Surprisingly, amyloid beta deposition was not associated with ICH when histopathology was available. Moreover, PACNS is not explicitly included in the etiological classification of spontaneous ICH. This issue has received little attention in the past, and it could be addressed in future prospective studies.

Neurological manifestations are frequent in patients with SARS-CoV-2 infection and can be correlated with different pathogenic mechanisms which can be divided into two categories: direct invasion of the central nervous system by the virus and indirect effects deriving from the severity of the systemic infection and by the inflammatory response correlated with cytokine storm. Among the neurological manifestations, acute encephalopathy is very frequent and its nomenclature has recently been updated. The occurrence of a condition of altered mental status, reduced consciousness, delirium up to coma represents an element associated with a greater severity of the infection and mortality both in an Intensive Care Unit setting and in an Emergency Department setting. The tissue damage mechanisms found in COVID-19 patients' encephalopathy and neuroimaging patterns, as well as histopathology, are similar to those described in sepsis-associated encephalopathy, further confirming the role of indirect mechanisms, with no CNS invasion by the virus. The available data have some limitations, notably the underuse of diagnostic neuroimaging techniques in severely affected patients, particularly in the first wave of the pandemic., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Objectives: To assess acute lipid profiles, atrial fibrillation and other cardiovascular risk factors in patients undergoing treatments by thrombectomy (EVT) with acute ischemic stroke (AIS)., Methods: We performed a retrospective analysis of the lipid profile and vascular risk factor in 1639 consecutive patients with acute ischemic stroke between January 2016 and December 2021. To assess lipid profiles, laboratory tests, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), were obtained the day after admission. We also examined the association between lipid profile, AF and EVT in multivariate logistic regression analysis., Results: Median age of patients was 74 years, 54.9% were males (95% CI 52.5-57.4%), and 26.8% (95% CI, 24.7-29.0%) had AF. EVT patients (n = 370; 22.57 %; 95% CI, 20.6-24.7) showed no difference in age (median 73 years (IQR; 63-80) versus 74 years (IQR; 63-82)), HbA1c levels (median 5.8 (IQR; 5.4-6.2) versus 5.9 (IQR; 5.4-6.4)), TG/HDL ratio (median 2.40 (IQR; 1.65-3.48) versus 2.51 (IQR; 1.73-3.64)), diabetes (OR 0.82; 95% CI 0.61 to 1.08), hypertension (OR 0.87; 95% CI 0.68 to 1.12) and obesity (OR 1.06; 95% CI 0.78 to 1.42) compared to non-EVT patients. Conversely, EVT patients showed lower levels of TC (160 mg/dl (IQR; 139- 187) versus 173 mg/dl (IQR; 148-202); p <0.001), LDL-C (105 mg/dl (IQR; 80-133) versus 113 mg/dl (IQR; 88-142); p <0.01), TG (98 mg/dl (IQR; 76-126) versus 107 mg/dl (IQR; 85-139); p <0.001), non-HDL-C (117 mg/dl (IQR; 94-145) versus 127 mg/dl (IQR; 103-154); p <0.001), HC (8.3 mmol/l (IQR; 6-11) versus 10 mmol/l (IQR; 7.3-13.5); p <0.001) than non-EVT patients. Multivariate logistic regression analysis showed an independent association of EVT with TC (OR 0.99, 95% CI 0.98-0.99), AF (OR 1.79, 95% CI 1.34-2.38), age (OR 0.98, 95% CI 0.96-0.99), and NIHSS (OR 1.17, 95% CI 0.14-1.19)., Conclusion: Total cholesterol and all cholesterol-related measures were significantly lower in patients undergoing thrombectomy than in other stroke patients. Conversely, we found that AF was significantly high in patients with EVT, suggesting that hypercholesterolemia could be mainly linked to small-vessel occlusion stroke while large vessel occlusion (LVO) stroke could show different causes. AIS patients may have different pathogenesis and their understanding may improve the discovery of specific and tailored preventive treatments., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: The aim of the present study was to assess emergency neurology management in Italy by comparing patients admitted to the hub and spoke hospitals., Methods: Data obtained from the annual Italian national survey (NEUDay) investigating the activity and facilities of neurology in the emergency room conducted in November 2021 were considered. Information for each patient who received a neurologic consultation after accessing the emergency room was acquired. Data on facilities were also gathered, including hospital classification (hub vs spoke), number of consultations, presence of neurology and stroke unit, number of beds, availability of neurologist, radiologist, neuroradiologist, and instrumental diagnostic accessibility., Results: Overall, 1,111 patients were admitted to the emergency room and had neurological consultation across 153 facilities (out of the 260 Italian ones). Hub hospitals had significantly more beds, availability of neurological staff, and instrumental diagnostic accessibility. Patients admitted to hub hospital had a greater need for assistance (higher number of yellow/red codes at neurologist triage). A higher propensity to be admitted to hub centers for cerebrovascular problems and to receive a diagnosis of stroke was observed., Conclusions: The identification of hub and spoke hospitals is strongly characterized by the presence of beds and instrumentation mainly dedicated to acute cerebrovascular pathologies. Moreover, the similarity in the number and type of accesses between hub and spoke hospitals suggests the need to look for adequate identification of all the neurological pathologies requiring urgent treatment., (© 2023. Fondazione Società Italiana di Neurologia.)

Introduction: We assessed best available data on access and delivery of acute stroke unit (SU) care, intravenous thrombolysis (IVT) and endovascular treatment (EVT) in the European region in 2019 and 2020., Patients and Methods: We compared national data per number of inhabitants and per 100 annual incident first-ever ischaemic strokes (AIIS) in 46 countries. Population estimates and ischaemic stroke incidence were based on United Nations data and the Global Burden of Disease Report 2019, respectively., Results: The estimated mean number of acute SUs in 2019 was 3.68 (95% CI: 2.90-4.45) per one million inhabitants (MIH) with 7/44 countries having less than one SU per one MIH. The estimated mean annual number of IVTs was 21.03 (95% CI: 15.63-26.43) per 100,000 and 17.14% (95% CI: 12.98-21.30) of the AIIS in 2019, with highest country rates at 79.19 and 52.66%, respectively, and 15 countries delivering less than 10 IVT per 100,000. The estimated mean annual number of EVTs in 2019 was 7.87 (95% CI: 5.96-9.77) per 100,000 and 6.91% (95% CI: 5.15-8.67) of AIIS, with 11 countries delivering less than 1.5 EVT per 100,000. Rates of SUs, IVT and EVT were stable in 2020. There was an increase in mean rates of SUs, IVT and EVT compared to similar data from 2016., Conclusion: Although there was an increase in reperfusion treatment rates in many countries between 2016 and 2019, this was halted in 2020. There are persistent major inequalities in acute stroke treatment in the European region. Tailored strategies directed to the most vulnerable regions should be prioritised.

I n the context of an adequate health care organization, the figure of the neurologist as an emergency operator (in the emergency room-ER-and/or in a dedicated outpatient clinic) is crucial for an effective functional connection with the territory (and therefore with general practitioners), a reduction in inappropriate ER accesses, specific diagnostic and therapeutic approaches to neurological emergencies in the ER and a reduction in nonspecific or even unnecessary instrumental investigations. In this position paper of the Italian Association of Emergency Neurology (ANEU: Associazione Neurologia dell'Emergenza Urgenza), these issues are addressed, and two important organizational solutions are proposed: 1) The Neuro Fast Track, as an outpatient organization approach strongly linked to general practitioners and non-neurological specialists and dedicated to cases with deferrable urgency (to be assessed within 72 h) 2) The identification of an emergency neurologist, who is engaged in ER assessments as a consultant and involved in the management of the semi-intensive care unit of the emergency neurology and the stroke unit according to an appropriate rotation, as well as in consultations for patients with neurological emergencies in inpatient wards The possibility of computerizing the screening of patients with deferrable urgency in the Neuro Fast Track is described. A dedicated app represents an important tool that can facilitate the identification of patients for whom deferred assessment is appropriate, the scheduling of neurological examinations and reductions in the booking time through a more rapid approach to specialist assessment and subsequent investigations., (© 2023. Fondazione Società Italiana di Neurologia.)

Cerebral collateral circulation is a network of blood vessels which stabilizes blood flow and maintains cerebral perfusion whenever the main arteries fail to provide an adequate blood supply, as happens in ischemic stroke. These arterial networks are able to divert blood flow to hypoperfused cerebral areas. The extent of the collateral circulation determines the volume of the salvageable tissue, the so-called " penumbra ". Clinically, this is associated with greater efficacy of reperfusion therapies (thrombolysis and thrombectomy) in terms of better short- and long-term functional outcomes, lower incidence of hemorrhagic transformation and of malignant oedema, and smaller cerebral infarctions. Recent advancements in brain imaging techniques (CT and MRI) allow us to study these anastomotic networks in detail and increase the likelihood of making effective therapeutic choices. In this narrative review we will investigate the pathophysiology, the clinical aspects, and the possible diagnostic and therapeutic role of collateral circulation in acute ischemic stroke.

Background: Thrombolysis (rTPA) and mechanical thrombectomy (MT) are cost-effective treatments for ischemic stroke. However, little is known about the impact of different types of health systems (HSs) on the outcome and cost of ischemic stroke., Methods: Literature search was performed on PubMed/OVID for studies without time limits. The year of publication, type of HS, cost of intervention treatment (rTPA/MT), cost of control strategy (conservative treatment or rTPA), quality-adjusted life years (QALYs) gained, and percentage of gross domestic product spent on health were recorded. The inclusion criteria were English literature, cost-effectiveness, and cost-utility analyses. The exclusion criterion was the absence of geographic coherence between the derived QALYs and the costs. The costs were inflated to 2021 and then converted to US dollar/euro. An analysis of variance or Kruskal-Wallis test was used to compare the percentage of cost reduction and the QALYs gained. Gross domestic product percentage was correlated with the QALYs gained., Results: Thirty-five studies were analyzed. No significant differences in the percentage of cost reduction were found among the different types of HS (Beveridge -14.74% [95% confidence interval {CI} -57.94/53.08] vs. Bismarck -2.27% [95% CI -122.73/118.18] vs. national insurance -0.015% [95% CI -16.96/51.00] vs. private insurance -4.05% [95% CI -32.62/13.18]). No differences were found in QALYs gained among the different HS (Beveridge 1021 [95% CI -36.37/1705.04] vs. Bismarck 440 [95% CI -2290.68/3870.68] vs. national insurance 643 [95% CI -137.54/2366.21] vs. private insurance 550 [95% CI 131.54/1128.06]). No differences were found among the QALYs gained between rTPA/conservative treatment versus rTPA/MT and rtPA + MT/MT. The percentage of gross domestic product spent on health did not correlate with the QALYs gained (rho = -0.16; P = 0.56)., Conclusions: MT and rTPA are independently cost-effective among different HS., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Anderson-Fabry disease (AFD) is an inherited lysosomal storage disorder characterized by a composite and multisystemic clinical phenotype and frequent involvement of the central nervous system (CNS). Research in this area has largely focused on the cerebrovascular manifestations of the disease, and very little has been described about further neurological manifestations, which are known in other lysosomal diseases, such as Gaucher disease. In particular, a clinical and neuroimaging phenotype suggesting neurodegeneration as a putative mechanism has never been fully described for AFD, but the increased survival of affected patients with early diagnosis and the possibility of treatment have given rise to some isolated reports in the literature on the association of AFD with a clinical phenotype of Parkinson disease (PD). The data are currently scarce, but it is possible to hypothesize the molecular mechanisms of cell damage that support this association; this topic is worthy of further study in particular in relation to the therapeutic possibilities, which have significantly modified the natural history of the disease but which are not specifically dedicated to the CNS. In this review, the molecular mechanisms underlying this association will be proposed, and the available data with implications for future research and treatment will be rewritten.

Acute onset quadriplegia with or without facial sparing is an extremely rare vascular syndrome, and the main focus of attention is on the cervical and upper thoracic spinal cord as the putative site of the damage. Quadriplegia has been occasionally reported in brainstem strokes within well-defined lesion patterns, but these reports have gained little attention so far because of the rarity of this clinical syndrome. The clinical, neuroanatomical and neuroimaging features of ischemic stroke locations associated with quadriplegia have been collected and reviewed in a pragmatical view, which includes a detailed description of the neurological signs associated with the damage of the pyramidal pathways. Two clinical examples have been added to raise practical suggestions in neurovascular practice. Ischemic stroke sites determining quadriplegia have some main well-defined midline locations in the brainstem, involving the pyramidal pathways of both sides in a single synchronous ischemic lesion in the medulla oblongata and in the pons. Several accompanying neurological signs have been described when the ischemic lesion involves tracts and nuclei other than the pyramidal pathways, and they can be useful as localizing clues. In some cases, the typical neuroimaging appearance of the ischemic lesion on Magnetic Resonance Imaging (MRI) has been reported as being a "heart appearance sign". This last sign has been described in midbrain strokes too, but this location is not associated with quadriplegia. The main etiology is atherothrombosis involving the intradural segment of the vertebral artery (VA) and their perforating branches. Two clinical examples of these rare vascular syndromes have been chosen to support a pragmatical discussion about the management of these cases. A midline ischemic stroke in the brainstem is a very rare vascular syndrome, and the acute onset quadriplegia is a distinctive feature of it. The awareness of this cerebrovascular manifestation might help to recognize and treat these patients.

Objective: The aetiologic diagnosis of non-traumatic acute myelopathies (AMs), and their differentiation from other mimicking conditions (i.e. 'mimics'), are clinically challenging, especially in the emergency setting. Here, we sought to identify: (i) red flags suggesting diagnoses alternative to AMs and (ii) clinical signs and magnetic resonance imaging (MRI) features differentiating non-compressive from compressive AMs., Materials and Methods: We retrospectively retrieved MRI scans of spinal cord dictated at emergency room from January 2016 to December 2020 in the suspicion of AMs. Patients with traumatic myelopathies and those with subacute/chronic myelopathies (i.e. MRI scans acquired >48 h from symptom onset) were excluded from analysis., Results: Our search retrieved 105 patients; after excluding 16 cases of traumatic myelopathies and 14 cases of subacute/chronic myelopathies, we identified 30 cases with non-compressive AMs, 30 cases with compressive AMs and 15 mimics. The presence of pyramidal signs ( p = 0.012) and/or pain ( p = 0.048) correctly identified 88% of cases with AMs. We failed to identify clinical indicators for distinguishing non-compressive and compressive AMs, although cases with inflammatory AMs were younger than cases with all the remaining conditions ( p < 0.05). Different MRI patterns could be described according to the final diagnosis: among non-compressive AMs, inflammatory lesions were more often posterior or central; vascular malformation had a fairly widespread distribution; spine ischaemia was more often central. Anterior or lateral compression were more often associated with neoplasms and disc herniation , whereas hemorrhages and infections produced spine compression on all sides., Conclusion: We propose a simple clinical indicator (i.e. pyramidal signs and/or pain) to distinguish AMs from their mimics in an emergency setting. Urgent spinal cord MRI remains essential to discriminate compressive and non-compressive aetiologies.

Background: Despite mounting evidence, the impact of the interplay between weather and pollution features on the risk of acute cardiac and cerebrovascular events has not been entirely appraised. The aim of this study was to perform a comprehensive cluster analysis of weather and pollution features in a large metropolitan area, and their association with acute cardiac and cerebrovascular events., Methods: Anonymized data on acute myocardial infarction (AMI) and acute cerebrovascular events were obtained from 3 tertiary care centers from a single large metropolitan area. Weather and pollution data were obtained averaging measurements from several city measurement stations managed by the competent regional agency for enviromental protection, and from the Metereological Center of Italian Military Aviation. Unsupervised machine learning was performed with hierarchical clustering to identify specific days with distinct weather and pollution features. Clusters were then compared for rates of acute cardiac and cerebrovascular events with Poisson models., Results: As expected, significant pairwise correlations were found between weather and pollution features. Building upon these correlations, hierarchical clustering, from a total of 1169 days, generated 4 separate clusters: mostly winter days with low temperatures and high ozone concentrations (cluster 1, N.=60, 5.1%), days with moderately high temperatures and low pollutants concentrations (cluster 2, N.=419, 35.8%), mostly summer and spring days with high temperatures and high ozone concentrations (cluster 3, N.=673, 57.6%), and mostly winter days with low temperatures and low ozone concentrations (cluster 4, N.=17, 1.5%). Overall cluster-wise comparisons showed significant differences in adverse cardiac and cerebrovascular events (P<0.001), as well as in cerebrovascular events (P<0.001) and strokes (P=0.001). Between-cluster comparisons showed that cluster 1 was associated with an increased risk of any event, cerebrovascular events, and strokes in comparison to cluster 2, cluster 3 and cluster 4 (all P<0.05), as well as AMI in comparison to cluster 3 (P=0.047). In addition, cluster 2 was associated with a higher risk of strokes in comparison to cluster 4 (P=0.030). Analysis adjusting for season confirmed the increased risk of any event, cerebrovascular events and strokes for cluster 1 and cluster 2., Conclusions: Unsupervised machine learning can be leveraged to identify specific days with a unique clustering of adverse weather and pollution features which are associated with an increased risk of acute cardiovascular events, especially cerebrovascular events. These findings may improve collective and individual risk prediction and prevention.

Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Recurrent stroke affects 9% to 15% of people within 1 year. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations on pharmacological management of blood pressure (BP), diabetes mellitus, lipid levels and antiplatelet therapy for the prevention of recurrent stroke and other important outcomes in people with ischaemic stroke or transient ischaemic attack (TIA). It does not cover interventions for specific causes of stroke, including anticoagulation for cardioembolic stroke, which are addressed in other guidelines. This guideline was developed through ESO standard operating procedures and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The working group identified clinical questions, selected outcomes, performed systematic reviews, with meta-analyses where appropriate, and made evidence-based recommendations, with expert consensus statements where evidence was insufficient to support a recommendation. To reduce the long-term risk of recurrent stroke or other important outcomes after ischaemic stroke or TIA, we recommend: BP lowering treatment to a target of <130/80 mmHg, except in subgroups at increased risk of harm; HMGCoA-reductase inhibitors (statins) and targeting a low density lipoprotein level of <1.8 mmol/l (70 mg/dl); avoidance of dual antiplatelet therapy with aspirin and clopidogrel after the first 90 days; to not give direct oral anticoagulant drugs (DOACs) for embolic stroke of undetermined source and to consider pioglitazone in people with diabetes or insulin resistance, after careful consideration of potential risks. In addition to the evidence-based recommendations, all or the majority of working group members supported: out-of-office BP monitoring; use of combination treatment for BP control; consideration of ezetimibe or PCSK9 inhibitors when lipid targets are not achieved; consideration of use of low-dose DOACs in addition to an antiplatelet in selected groups of people with coronary or peripheral artery disease and aiming for an HbA1c level of <53 mmol/mol (7%) in people with diabetes mellitus. These guidelines aim to standardise long-term pharmacological treatment to reduce the burden of recurrent stroke in Europe., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: All authors have completed a declaration of competing interests and details are available in Supplemental Table 1., (© European Stroke Organisation 2022.)

The association between atrial fibrillation (AF), acute coronary syndrome (ACS), and stroke is a complex scenario in which the assessment of both thrombotic and hemorrhagic risk is necessary for scheduling an individually tailored therapeutic plan. Recent clinical trials investigating new antithrombotic drugs and dual and triple pathways in high-risk cardiovascular patients have revealed a new therapeutic scenario. In this paper, we review the burden of ischemic stroke (IS) in patients post-myocardial infarction with and without atrial fibrillation and the possible therapeutic strategies from a stroke point of view.

Background: Despite mounting evidence, there is uncertainty on the impact of the interplay between weather and pollution features on the risk of acute cerebrovascular events (CVE). We aimed at appraising role of weather and pollution on the daily risk of CVE., Methods: Anonymized data from a hub CVE center in a large metropolitan area were collected and analyzed according to weather (temperature, pressure, humidity, and rainfall) and pollution (carbon monoxide [CO], nitrogen dioxide [NO2], nitrogen oxides [NOX], ozone [O3], and particulate matter [PM]) on the same and the preceding days. Poisson regression and time series analyses were used to appraise the association between environmental features and daily CVE, distinguishing also several subtypes of events., Results: We included a total of 2534 days, with 1363 days having ≥1 CVE, from 2012 to 2017. Average daily rate was 1.56 (95% confidence interval: 1.49; 1.63) for CVE, with other event rates ranging between 1.42 for stroke and 0.01 for ruptured intracranial aneurysm. Significant associations were found between CVE and temperature, pressure, CO, NO2, NOX, O3, and PM <10 µm (all P<0.05), whereas less stringent associations were found for humidity, rainfall, and PM <2.5 µm. Time series analysis exploring lag suggested that associations were stronger at same-day analysis (lag 0), but even environmental features predating several days or weeks were significantly associated with events. Multivariable analysis suggested that CO (point estimate 1.362 [1.011; 1.836], P=0.042) and NO2 (1.011 [1.005; 1.016], P<0.001) were the strongest independent predictors of CVE., Conclusions: Environmental features are significantly associated with CVE, even several days before the actual event. Levels of CO and NO2 can be potentially leveraged for population-level interventions to reduce the burden of CVE.

Objective: The goal of this study is to understand how very elderly patients (VEP) after ischemic stroke are currently treated in a Stroke Unit (SU) Hub in Italy. We designed a retrospective monocentric study on patients admitted in the SU of "AO San Camillo Forlanini" over an 8-year period., Material and Methods: Data were collected among patients with acute ischemic stroke admitted to SU between January 2012 and December 2019. Patients were divided into three sub-groups: Adults (18-65 years); Elderly (66-85 years); and VEP (>85 years). Vascular risk factors and clinical variables as predictors of short-term clinical outcome were compared among age groups., Results: A total of 1979 patients were enrolled, 254 were VEP (12.8%). The proportion of VEP showed no significant modifications during the 8-year period (11.9% in 2012-2015 and 13.7% in 2016-2019; p=0.93). The proportion of women, hypertension and atrial fibrillation was significantly higher in VEP compared to other age groups (p<0.001). The rate of VEP being treated with rt-PA increased from 2012-2015 to 2016-2019 (from 12.8% to 25.5%, p<0.001). Endovascular thrombectomy was rarely performed in VEP (1.5% of VEP). Rt-PA treatment was associated with favorable outcome for all three age groups (p<0.05)., Conclusions: We showed that VEP present different vascular risk factor profiles, clinical features, and prognostic elements for short-term stroke outcome. Future studies will reveal whether we will observe an increasing trend in the use of rt-PA and endovascular thrombectomy and whether it will result in improved functional outcome for VEP., Competing Interests: Declaration of Competing Interest Authors have no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Aim of the Work: We present a case of a woman affected by nonconvulsive status epilepticus (NCSE) caused by cerebral hyperperfusion syndrome (CHS) after carotid endarterectomy (CEA) who was successfully treated with Brivaracetam (BRV) administered via nasogastric tube (NGT)., Case Presentation: An 82-years old woman was referred for increasing blood pressure, severe headache and two focal motor seizures on postoperative day four after right CEA. CT scan showed edema of the right hemisphere with a midline shift of 5 mm. The patient underwent daily Electroencephalography (EEG) monitoring which showed continuous epileptiform discharges over the right hemisphere, compatible with a diagnosis of status epilepticus. She was treated with standard antiepileptic drugs (Phenytoin, Lacosamide and Levetiracetam iv) without clinical response. A therapeutic trial with BRV 200mg administered via nasogastric tube (NGT) was tried which resulted in substantial clinical benefit., Conclusions: The administration of new antiepileptic drugs (AEDs) such as BRV may result in significant clinical improvement in refractory cases of status epilepticus. The enteral administration of AEDs via NGT should always be considered for refractory cases of status epilepticus when standard iv treatment has failed or is not possible.

Purpose of Review: The European Stroke Organisation published a European Stroke Action Plan (SAP-E) for the years 2018-2030. The SAP-E addresses the entire chain of care from primary prevention through to life after stroke. Within this document digital health tools are suggested for their potential to facilitate greater access to stroke care. In this review, we searched for digital health solutions for every domain of the SAP-E., Recent Findings: Currently available digital health solutions for the cerebrovascular disease have been designed to support professionals and patients in healthcare settings at all stages. Telemedicine in acute settings has notably increased the access to tissue plasminogen activator and thrombectomy whereas in poststroke settings it has improved access to rehabilitation. Moreover, numerous applications aim to monitor vital signs and prescribed treatment adherence., Summary: SAP-E with its seven domains covers the whole continuum of stroke care, where digital health solutions have been considered to provide utility at a low cost. These technologies are progressively being used in all phases of stroke care, allowing them to overcome geographical and organizational barriers. The commercially available applications may also be used by patients and their careers in various context to facilitate accessibility to health improvement strategies., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: To describe the background, principles and implementation of the Stroke Action Plan for Europe 2018--2030 (SAP-E) in the perspective of the current COVID-19 pandemic., Recent Findings: SAP-E sets targets for the implementation of evidence-based preventive actions and stroke services to 2030. A recent mapping of stroke care in Europe has documented massive inequalities and even in high-income European countries access to reperfusion therapy and mortality after ischaemic stroke varies significantly. Organized stroke care providing stroke unit care and access to reperfusion therapies reduces mortality and long-term disability. Stroke prevention and care are highly cost-effective. The COVID-19 pandemic has challenged organized care, diverged attention from stroke and necessitated a novel approach to the implementation program because of the continued need for social distancing and reduced travelling. Consequently, meetings, training and engagement will be handled by online resources., Summary: Stroke can be prevented and treated but there remain massive inequalities in Europe. SAP-E has set targets for development of stroke care. COVID-19 pandemic has led to further challenges for stroke care and implementation of the Action Plan will rely on online meetings and resources as it is yet unforeseeable when things will return to normal., Video Abstract: http://links.lww.com/CONR/A53., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To analyse structural and non-structural modifications of acute stroke care pathways undertaken at healthcare institutions across the regions of Italy due to the coronavirus disease 2019 (COVID-19) pandemic., Methods: Research on National decrees specific for the pandemic was carried out. The stroke pathways of four Italian regions from North to South, such as Lombardy, Veneto, Lazio and Campania, were analysed before and after the pandemic outbreak., Findings: On 29 February 2020, the Italian Minister of Health issued national guidelines on how to address the COVID-19 emergency. Stroke management was affected and required changes, basically resulting in the need to prioritise the ongoing COVID-19 emergency. In the most affected regions, the closure of departments and hospitals led to a complete reorganisation of previously functioning stroke networks. With the closure of several Stroke Units and Stroke Centres, the transportation time to hospital lengthened significantly, especially for the outlying populations., Discussion: The COVID-19 pandemic outbreak has been spreading rapidly in Italy and placing an overwhelming burden on healthcare systems. In response to this, political and healthcare decision-makers worked together to develop and implement efforts to sustain the national healthcare system while fighting the pandemic. Stroke care pathways changed during the pandemic and different organisational models were applied in the most affected regions., Conclusions: Stroke treatment pathways will need to be redesigned so to guarantee that severe and acute disease patients do not lose their rights to the access and delivery of care during the COVID-19 pandemics., (© European Stroke Organisation 2020.)

Introduction: Despite the availability of prevention and therapies of stroke, their implementation in clinical practice, even of low-cost ones, remains poor. In 2015, the European Stroke Organisation (ESO) initiated the ESO Enhancing and Accelerating Stroke Treatment (EAST) program, which aims to improve stroke care quality, primarily in Eastern Europe. Here, we describe its methods and milestones., Patients and Methods: The ESO EAST program is using an implementation strategy based on a 'detecting-understanding-reducing disparities' conceptual framework: stroke care quality is first measured (after developing a platform for data collection), gaps are identified in the current service delivery, and ultimately feedback is provided to participating hospitals, followed by the application of interventions to reduce disparities. The ESO EAST program is carried out by establishing a stroke quality registry, stroke management infrastructure, and creating education and training opportunities for healthcare professionals., Results: Program management and leadership infrastructure has been established in 19 countries (Country Representatives in 22 countries, National Steering Committee in 19 countries). A software platform for data collection and analysis: Re gistry of S troke Care Q uality was developed, and launched in 2016, and has been used to collect data from over 90,000 patients from >750 hospitals and 56 countries between September 2016 and May 2019. Training in thrombolysis, nursing and research skills has been initiated., Discussion: ESO EAST is the first pan-Eastern European (and beyond) multifaceted quality improvement intervention putting evidence-informed policies into practice. Continuous monitoring of stroke care quality allows hospital-to-hospital and country-to-country benchmarking and identification of the gaps and needs in health care., (© European Stroke Organisation 2020.)