Calcitonin Gene-Related Peptide Systemic Effects: Embracing the Complexity of Its Biological Roles-A Narrative Review.

The calcitonin gene-related peptide (CGRP) is a neuropeptide widely distributed throughout the human body. While primarily recognized as a nociceptive mediator, CGRP antagonists are currently utilized for migraine treatment. However, its role extends far beyond this, acting as a regulator of numerous biological processes. Indeed, CGRP plays a crucial role in vasodilation, inflammation, intestinal motility, and apoptosis. In this review, we explore the non-nociceptive effects of CGRP in various body systems, revealing actions that can be contradictory at times. In the cardiovascular system, it functions as a potent vasodilator, yet its antagonists do not induce arterial hypertension, suggesting concurrent modulation by other molecules. As an immunomodulator, CGRP exhibits intriguing complexity, displaying both anti-inflammatory and pro-inflammatory effects. Furthermore, CGRP appears to be involved in obesity development while paradoxically reducing appetite. A thorough investigation of CGRP's biological effects is crucial for anticipating potential side effects associated with its antagonists' use and for developing novel therapies in other medical fields. In summary, CGRP represents a neuropeptide with a complex systemic impact, extending well beyond nociception, thus offering new perspectives in medical research and therapeutics.

Recurrent paraneoplastic cerebral hemorrhage in lung cancer: A case report.

Cerebral hemorrhage management in a patient requiring anticoagulant therapy is a therapeutic challenge also due to the absence of guidelines that convincingly define the best therapeutic strategy. Although the occurrence of cerebral hemorrhage in a patient with anticoagulant therapy seems to make the bleeding etiology obvious, sometimes, it is better to reflect on other possible causes and set up an adequate diagnostic workup. Herein, we describe a case of a 73-year-old male patient with atrial fibrillation, mechanical heart valve, and pacemaker that experienced an ischemic minor stroke during steady anticoagulation therapy with recurrent intracerebral haemorrhages (ICHs).

The Pathophysiology of Collateral Circulation in Acute Ischemic Stroke.

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.

A smart devices based secondary prevention program for cerebrovascular disease patients.

Background: Commercially available health devices are gaining momentum and represent a great opportunity for monitoring patients for prolonged periods. This study aimed at testing the feasibility of a smart device-based secondary prevention program in a cohort of patients with cryptogenic stroke. Methods: In this proof-of-principle study, patients with non-disabling ischemic stroke and transient ischemic attacks (TIA) in the subacute phase were provided with a smartwatch and smart devices to monitor several parameters - i.e., oxygen saturation, blood pressure, steps a day, heart rate and heart rate variability - for a 4-week period (watch group). This group was compared with a standard-of-care group. Our primary endpoint was the compliance with the use of smart devices that was evaluated as the number of measures performed during the observation period. Results: In total, 161 patients were recruited, 87 in the WATCH group and 74 in the control group. In the WATCH group, more than 90% of patients recorded the ECG at least once a day. In total, 5,335 ECGs were recorded during the study. The median blood pressure value was 132/78 mmHg and the median oxygen saturation value was 97%. From a clinical standpoint, although not statistically significant, nine atrial fibrillation episodes (10.3%) in the WATCH group vs. 3 (4%) in the control group were detected. Conclusion: Our study suggests that prevention programs for cerebrovascular disease may benefit from the implementation of new technologies.

Treating Post-stroke Epilepsy in a Patient With Multiple Comorbidities.

Stroke is a major cause of seizures and epilepsy in adults. Stroke severity, younger age, hemorrhagic subtype of stroke, and alcohol use have been identified as risk factors for the development of stroke-related epilepsy. Despite being a common complication in stroke survivors, current guidelines do not provide strong recommendations about the optimal treatment of post-stroke seizures. No clear guidance is given about the preferred antiseizure medications (ASMs), primary and secondary prophylaxis, and ASMs withdrawal. The management of older patients is further complicated by the presence of comorbidities, pharmacokinetic alterations, and intake of several medications. We present a case of a 77-year-old man affected by epidermolysis bullosa and diabetes mellitus, who suffered from ischemic stroke and then developed post-stroke seizures. This case shows how complex it is to manage post-stroke seizures in an older patient with multiple comorbidities.

Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome in patients with COVID-19 infection: is there a link? A systematic review and case report analysis.

During the SARS-CoV2 pandemic, several cases of Posterior Reversible Encephalopathy Syndrome (PRES) and of Reversible Cerebral Vasoconstriction Syndrome (RCVS) in COVID-19 patients have been reported, but the link between these syndromes and COVID-19 is unclear. We performed a systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to evaluate whether SARS-CoV2 infection or the drugs used to treat it could be deemed potential risk factors for PRES or RCVS. We performed a literature search. We found 70 articles (60 on PRES and 10 on RCVS) concerning n = 105 patients (n = 85 with PRES, n = 20 with RCVS). We analyzed the clinical characteristics of the two populations separately, then performed an inferential analysis to search for other independent risk factors. We found fewer than usual PRES-related (43.9%) and RCVS-related (45%) risk factors in patients with COVID-19. Such a low incidence of risk factors for PRES and RCVS might suggest the involvement of COVID-19 as an additional risk factor for both diseases due to its capability to cause endothelial dysfunction. We discuss the putative mechanisms of endothelial damage by SARS-CoV2 and antiviral drugs which may underlie the development of PRES and RCVS.

Smartphone App in Stroke Management: A Narrative Updated Review.

The spread of smartphones and mobile-Health (m-health) has progressively changed clinical practice, implementing access to medical knowledge and communication between doctors and patients. Dedicated software called Applications (or Apps), assists the practitioners in the various phases of clinical practice, from diagnosis to follow-up and therapy management. The impact of this technology is even more important in diseases such as stroke, which are characterized by a complex management that includes several moments: primary prevention, acute phase management, rehabilitation, and secondary prevention. This review aims to evaluate and summarize the available literature on Apps for the clinical management of stroke. We described their potential and weaknesses, discussing potential room for improvement. Medline databases were interrogated for studies concerning guideline-based decision support Apps for stroke management and other medical scenarios from 2007 (introduction of the first iPhone) until January 2022. We found 551 studies. Forty-three papers were included because they fitted the scope of the review. Based on their purpose, Apps were classified into three groups: primary prevention Apps, acute stroke management Apps, and post-acute stroke Apps. We described the aim of each App and, when available, the results of clinical studies. For acute stroke, several Apps have been designed with the primary purpose of helping communication and sharing of patients' clinical data among healthcare providers. However, interactive systems Apps aiming to assist clinicians are still lacking, and this field should be developed because it may improve stroke patients' management.

Color-coded multiphase computed tomography angiography may predict outcome in anterior circulation acute ischemic stroke.

PURPOSE: To evaluate whether arterial and venous color-coded mCTA score may predict clinical outcome in anterior circulation acute ischemic stroke. METHODS: Consecutive patients referred to the emergency department with anterior circulation acute ischemic stroke (AIS) were retrospectively reviewed at our center. All patients underwent multimodal brain computed tomography (CT) imaging, including non-contrast CT (NCCT) and multiphase computed tomography angiography (mCTA). Baseline collateral scores of color-coded mCTA, also known as ColorViz, and conventional mCTA were recorded. mCTA was assessed by a 6-point scale whereas color-coded mCTA was assessed by a 3-point scale. In the Color-coded maps, a different color is assigned to intracranial vessels based on the arrival time of the contrast medium and on a per-person adaptive threshold technique. We compared the radiological and clinical features of a group of patients who reached independency (defined as modified Rankin Scale score ≤ 2) with those of patients who did not. A multivariate logistic regression model was then used to assess the potential of color-coded mCTA scores to predict patients' outcome after AIS. RESULTS: A total of 86 patients (36 M, 50 F) were enrolled in the study. Multivariate logistic regression showed that score 3 at Color-coded mCTA was a good predictor of favorable outcome (p = 0.003). Moreover, NIHSS at onset (p = 0.004) and discharge (p < 0.001) along with ischemic core area (p = 0.011) were significant predictors of favorable prognosis. CONCLUSION: our data confirm that ColorViz is a useful and easily understandable neuroimaging tool that might have a predictive role in assessing the outcome of anterior circulation acute ischemic stroke patients regardless of revascularization therapy.

New Perspectives in Stroke Management: Old Issues and New Pathways.

Stroke is a leading cause of disability and death worldwide and social burden is huge in terms of disabilities, mortality and healthcare costs. Recently, in an acute stroke setting, renewed interest in disease-modifying therapies and novel approaches has led to enhanced recovery and the reduction of long-term disabilities of patients who suffered a stroke. In the last few years, the basic principle "time is brain" was overcome and better results came through the implementation of novel neuroimaging tools in acute clinical practice, allowing one to extend acute treatments to patients who were previously excluded on the basis of only a temporal selection. Recent studies about thrombectomy have allowed the time window to be extended up to 24 h after symptoms onset using advanced neuroradiological tools, such as computer tomography perfusion (CTP) and magnetic resonance imaging (MRI) to select stroke patients. Moreover, a more effective acute management of stroke patients in dedicated wards (stroke units) and the use of new drugs for stroke prevention, such as novel oral anticoagulants (NOACs) for atrial fibrillation, have allowed for significant clinical improvements. In this editorial paper, we summarize the current knowledge about the main stroke-related advances and perspectives and their relevance in stroke care, highlighting recent developments in the definition, management, treatment, and prevention of acute and chronic complications of stroke. Then, we present some papers published in the Special Issue "Clinical Research on Ischemic Stroke: Novel Approaches in Acute and Chronic Phase".