Exploring vertebral artery stump syndrome: An overlooked cause of posterior ischemic strokes. A narrative review of current management options.

INTRODUCTION: Stump syndrome is defined as a clinical syndrome resulting from a distal intracranial vessel embolic stroke due to an extracranial vessel occlusion. Similar to the anterior circulation, the recurrence of ischemic strokes in territories supplied by the posterior circulation in the presence of vertebral artery occlusion is termed Vertebral Artery Stump Syndrome (VASS). MATERIAL AND METHODS: We conducted a literature review, identifying 72 patients with transient ischemic attacks (TIAs) or ischemic strokes attributed to VASS, according to Kawano criteria. We categorized all patients in two groups focusing on the therapeutic management those who underwent primary medical treatment and those who received endovascular or surgical treatment either in acute or chronic phase. RESULTS: In the anticoagulant therapy group, only 1 patient had a stroke recurrence. Among the 4 on antiplatelets, all had recurrences, but 3 benefited from switching to anticoagulants or endovascular therapy. In the endovascular therapy group, worse outcomes were linked to acute large vessel occlusion. Endovascular treatment of the vertebral artery, in a chronic phase, was explored in literature for recurrent TIAs or minor strokes suggesting that this could be a viable therapeutic alternative when medical treatment failed in preventing recurrence of ischemic stroke. CONCLUSIONS: Some studies suggest that anticoagulant medical therapy may be beneficial for VASS and endovascular therapy has also been reported for selected patients. However, data on treatment outcomes and prognosis are still underreported, making treatment decisions challenging. Randomized Controlled Trials are needed to establish the optimal treatment approach.

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.

Unlocking the Potential of Stroke Blood Biomarkers: Early Diagnosis, Ischemic vs. Haemorrhagic Differentiation and Haemorrhagic Transformation Risk: A Comprehensive Review.

Stroke, a complex and heterogeneous disease, is a leading cause of morbidity and mortality worldwide. The timely therapeutic intervention significantly impacts patient outcomes, but early stroke diagnosis is challenging due to the lack of specific diagnostic biomarkers. This review critically examines the literature for potential biomarkers that may aid in early diagnosis, differentiation between ischemic and hemorrhagic stroke, and prediction of hemorrhagic transformation in ischemic stroke. After a thorough analysis, four promising biomarkers were identified: Antithrombin III (ATIII), fibrinogen, and ischemia-modified albumin (IMA) for diagnostic purposes; glial fibrillary acidic protein (GFAP), micro RNA 124-3p, and a panel of 11 metabolites for distinguishing between ischemic and hemorrhagic stroke; and matrix metalloproteinase-9 (MMP-9), s100b, and interleukin 33 for predicting hemorrhagic transformation. We propose a biomarker panel integrating these markers, each reflecting different pathophysiological stages of stroke, that could significantly improve stroke patients' early detection and treatment. Despite promising results, further research and validation are needed to demonstrate the clinical utility of this proposed panel for routine stroke treatment.

Argyria and Neuropsychiatric Disorders: When not only the Matter is Gray. A Literature Review and a Case Report.

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.

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.

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).

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.

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.

Neurophysiology tools to lower the stroke onset to treatment time during the golden hour: microwaves, bioelectrical impedance and near infrared spectroscopy.

Reperfusion therapy administration timing in acute ischaemic stroke is the main determinant of patients' mortality and long-term disability. Indeed, the first hour from the stroke onset is defined the "golden hour", in which the treatment has the highest efficacy and lowest side effects. Delayed ambulance transport, inappropriate triage and difficulty in accessing CT scans lead to delayed onset to treatment time (OTT) in clinical practice. To date brain CT scan is needed to rule out intracranial haemorrhage, which is a major contraindication to thrombolytic therapy. The availability, dimension and portability make CT suitable mainly for intrahospital use, determining further delays in the therapies administration. This review aims at evaluating portable neurophysiology technologies developed with the scope of speeding up the diagnostic phase of acute stroke and, therefore, the initiation of intravenous thrombolysis. Medline databases were explored for studies concerning near infrared spectroscopy (NIRS), bioelectrical impedance spectroscopy (BIS) and Microwave imaging (MWI) as methods for stroke diagnosis. A total of 1368 articles were found, and 12 of these fit with our criteria and were included in the review. For each technology, the following parameters were evaluated: diagnostic accuracy, ability to differentiate ischaemic and haemorrhagic stroke, diagnosis time from stroke onset, portability and technology readiness level (TRL). All the described methods seem to be able to identify acute stroke even though the number of studies is very limited. Low cost and portability make them potentially usable during ambulance transport, possibly leading to a reduction of stroke OTT along with the related huge benefits in terms of patients outcome and health care costs. In addition, unlike standard imaging techniques, neurophysiological techniques could allow continuous monitoring of patients for timely intrahospital stroke diagnosis.KEY MESSAGESFirst hour from the stroke onset is defined the "golden hour", in which the treatment has the highest efficacy and lowest side effects.The delay for stroke onset to brain imaging time is one of the major reasons why only a minority of patients with acute ischaemic stroke are eligible to reperfusion therapies.Neurophysiology techniques (NIRS, BIS and MWI) could have a potential high impact in reducing the time to treatment in stroke patients.

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.