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New Frontiers in the Clinical Management of Stroke

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Neurology".

Deadline for manuscript submissions: closed (30 August 2022) | Viewed by 49698

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Special Issue Editors

Dr. Maria Luisa Zedde

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Neurology Unit, Stroke Unit, Department of Neuromotor Physiology and Rehabilitation, Azienda Unità Sanitaria Locale – IRCCS di Reggio Emilia, Reggio Emilia, Italy
Interests: stroke; neuroimaging; neurointerventional; angiography; rare neurovascular disorders; small vessel disease
Special Issues, Collections and Topics in MDPI journals

Dr. Rosario Pascarella

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Guest Editor

IRCCS Azienda Unità Sanitaria Locale di Reggio Emilia, Reggio Emilia, Italy
Interests: neuroimaging; stroke; small vessel disease; rare neurovascular diseases; cerebral hemorrhage; acute stroke treatment

Special Issue Information

Dear Colleagues,

Unfortunately, stroke is a frequent condition, but not all the causes of cerebrovascular diseases are really frequent. Rare diseases are individually rare but collectively frequent, and among the several hundreds of causes of stroke, vascular neurologists frequently consider and look for rare diseases. The main topic of this Special Issue can be detailed considering a pragmatic approach to raising suspicion, distinguishing between subcategories of diseases, and performing the most appropriate diagnostic pathway in order to define the treatment, when available. Rare neurovascular disorders are often very good mimics of frequent conditions, both in clinical presentation and in neuroimaging pattern, but they exist, and many of them are probably largely undiagnosed because we rarely think of them. For example, monogenic causes of small vessel diseases have excellent phenocopies in frequent sporadic disorders (e.g., “hypertensive” small vessel disease, cerebral amyloid angiopathy or mixed small vessel diseases), and the main rare diseases can coexist with frequent diseases (e.g., atrial fibrillation, arterial hypertension, smoking habitus, diabetes). On the other side, non-atheromasic large vessel diseases range from vasculitides to dysplasic and/or dissecative arteriopathies. Another main issue is that “rare” does not mean “hereditary” or genetic, but this is a point frequently raised by patients and relatives, and it is not always easy to give a definite answer. Finally, rare diseases are often unique, so they represent a field where even single case may be relevant.

I hope many of you can contribute to this Special Issue by sharing your hypotheses and findings.

Dr. Maria Luisa Zedde
Dr. Rosario Pascarella
Guest Editors

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Keywords

rare neurovascular disorders
monogenic small vessel diseases
spontaneous dissection
fibromuscular dysplasia
CADASIL
carotid web
PACNS
Anderson–Fabry disease
mitochondrial disorders

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Published Papers (12 papers)

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13 pages, 1250 KiB

Open AccessArticle

Transient Global Amnesia (TGA): Sex-Specific Differences in Blood Pressure and Cerebral Microangiopathy in Patients with TGA

by Andreas Rogalewski, Anne Beyer, Anja Friedrich, Frédéric Zuhorn, Randolf Klingebiel, Friedrich G. Woermann, Sabine Oertelt-Prigione and Wolf-Rüdiger Schäbitz

J. Clin. Med. 2022, 11(19), 5803; https://doi.org/10.3390/jcm11195803 - 30 Sep 2022

Cited by 2 | Viewed by 2688

Abstract

Transient global amnesia (TGA) is defined by an acute memory disturbance of unclear aetiology for a period of less than 24 h. Observed psychological, neuroanatomical and hormonal differences between the sexes in episodic memory suggest sex-specific differences in memory disorders such as TGA. The aim of this study was to determine sex-specific differences in cardiovascular risk profiles, recurrences and magnetic resonance imaging (MRI). In total, 372 hospitalised TGA patients between 01/2011 and 10/2021 were retrospectively analysed. Comparisons were made between female and male TGA patients and compared to 216 patients with acute stroke. In our sample, women were overrepresented (61.8%), especially compared to the general population in the 65–74 age category (χ² = 10.6, p < 0.02). On admission, female TGA patients had significantly higher systolic blood pressure values and a higher degree of cerebral microangiopathy compared to male TGA patients, whereas acute stroke patients did not. No sex-specific differences were observed with respect to recurrences or hippocampal DWI lesions. Our data demonstrate sex-specific differences in TGA. The higher blood pressure on admission and different degree of cerebral microangiopathy in female TGA patients supports the theory of blood pressure dysregulation as a disease trigger. Distinct precipitating events in female and male patients could lead to differences in the severity and duration of blood pressure abnormalities, possibly explaining the higher incidence in female patients. Full article

(This article belongs to the Special Issue New Frontiers in the Clinical Management of Stroke)

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13 pages, 2291 KiB

Open AccessArticle

Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and Hyperglycemia

by Sarah Gelhard, Roxane-Isabelle Kestner, Moritz Armbrust, Helmuth Steinmetz, Christian Foerch and Ferdinand O. Bohmann

J. Clin. Med. 2022, 11(12), 3343; https://doi.org/10.3390/jcm11123343 - 10 Jun 2022

Viewed by 3075

Abstract

(1) Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke is limited because of several contraindications. In routine clinical practice, patients with a recent stroke are typically not treated with rt-PA in case of a recurrent ischemic event. The same applies to its use in the context of pulmonary artery embolism and myocardial infarction with a recent stroke. In this translational study, we evaluated whether rt-PA treatment after experimental ischemic stroke with or without additional hyperglycemia increases the risk for hemorrhagic transformation (HT) and worsens functional outcome regarding the old infarct area. (2) In total, 72 male C57BL/6N mice were used. Ischemic stroke (index stroke) was induced by transient middle cerebral artery occlusion (tMCAO). Mice received either rt-PA or saline 24 h or 14 days after index stroke to determine whether a recent ischemic stroke predisposes to HT. In addition to otherwise healthy mice, hyperglycemic mice were analyzed to evaluate diabetes as a second risk factor for HT. Mice designated to develop hyperglycemia were pre-treated with streptozotocin. (3) The neurological outcome in rt-PA and saline-treated normoglycemic mice did not differ significantly, either at 24 h or at 14 days. In contrast, hyperglycemic mice treated with rt-PA had a significantly worse neurological outcome (at 24 h, p = 0.02; at 14 days, p = 0.03). At 24 h after rt-PA or saline treatment, HT scores differed significantly (p = 0.02) with the highest scores within hyperglycemic mice treated with rt-PA, where notably only small petechial hemorrhages could be detected. (4) Thrombolysis after recent ischemic stroke does not increase the risk for HT or worsen the functional outcome in otherwise healthy mice. However, hyperglycemia as a second risk factor leads to neurological deterioration after rt-PA treatment, which cannot be explained by an increase of HT alone. Direct neurotoxic effects of rt-PA may play a role. Full article

(This article belongs to the Special Issue New Frontiers in the Clinical Management of Stroke)

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9 pages, 896 KiB

Open AccessArticle

Multiple Arterial Dissections and Connective Tissue Abnormalities

by Philipp Erhart, Daniel Körfer, Susanne Dihlmann, Jia-Lu Qiao, Ingrid Hausser, Peter Ringleb, Jörg Männer, Nicola Dikow, Christian P. Schaaf, Caspar Grond-Ginsbach and Dittmar Böckler

J. Clin. Med. 2022, 11(12), 3264; https://doi.org/10.3390/jcm11123264 - 7 Jun 2022

Cited by 9 | Viewed by 8785

Abstract

Background: Although patients with multiple arterial dissections in distinct arterial regions rarely present with known connective tissue syndromes, we hypothesized that mild connective tissue abnormalities are common findings in these patients. Methods: From a consecutive register of 322 patients with cervical artery dissection (CeAD), we identified and analyzed 4 patients with a history of additional dissections in other vascular beds. In three patients, dermal connective tissue was examined by electron microscopy. DNA from all four patients was studied by whole-exome sequencing and copy number variation (CNV) analysis. Results: The collagen fibers of dermal biopsies were pathologic in all three analyzed patients. One patient carried a CNV disrupting the COL3A1 and COL5A2 genes (vascular or hypermobility type of Ehlers–Danlos syndrome), and another patient a CNV in MYH11 (familial thoracic aortic aneurysms and dissections). The third patient carried a missense substitution in COL5A2. Conclusion: Three patients showed morphologic alterations of the dermal connective tissue, and two patients carried pathogenic variants in genes associated with arterial connective tissue dysfunction. The findings suggest that genetic testing should be recommended after recurrent arterial dissections, independently of apparent phenotypical signs of connective tissue disorders. Full article

(This article belongs to the Special Issue New Frontiers in the Clinical Management of Stroke)

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7 pages, 780 KiB

Open AccessArticle

Increased Prognostic Yield by Combined Assessment of Non-Contrast Computed Tomography Markers of Antithrombotic-Related Spontaneous Intracerebral Hemorrhage Expansion

by Aristeidis H. Katsanos, Himanshu Gupta, Andrea Morotti, Simon Beshara, Tushar Patil, Saeed Al-Zahrani, Georgios Tsivgoulis, Dariush Dowlatshahi, Joshua N. Goldstein, Andreas Charidimou and Ashkan Shoamanesh

J. Clin. Med. 2022, 11(6), 1596; https://doi.org/10.3390/jcm11061596 - 14 Mar 2022

Cited by 1 | Viewed by 2030

Abstract

Background and aims: The utility of proposed non-contrast computed tomography (NCCT) markers for the prediction of hematoma expansion in patients with antithrombotic-related spontaneous intracerebral hemorrhage (ICH) is limited. Additionally, there is significant overlap between different suggested ICH shape and density markers. Methods: We assessed the prognostic yield for hematoma expansion of a combined score incorporating features of ICH shape irregularity (satellite sign and/or Barras score ≥ 3), heterogeneous ICH density (swirl sign and/or Barras score ≥ 3) on baseline NCCT and timing from ICH onset to NCCT. Results: We evaluated data from 79 patients with antithrombotic-related spontaneous ICH (32% with hematoma expansion). Swirl (84% vs. 39%) and satellite signs (20% vs. 7%) on baseline NCCT were significantly more prevalent (p < 0.001) in patients with hematoma expansion. Patients with hematoma expansion had more irregular and heterogeneous bleeds on baseline NCCT scans, as quantified by higher (p < 0.001) Barras shape (4 (4–5) vs. 3 (2–4)) and density scores (4 (3–5) vs. 2 (1–3)), respectively. The overall diagnostic yield of the combined score (area under the curve: 0.86, 95%CI: 0.78–0.94) significantly outperformed (p < 0.001) the diagnostic yield of each individual marker. Scores of 4 or 5 in the combined score were associated with a sensitivity of 60.0%, specificity of 90.7%, overall diagnostic accuracy of 81.0%, positive likelihood ratio (LR) of 6.48, negative LR of 0.44, positive predictive value (PV) of 0.76 and negative PV of 0.83. Conclusion: Combined NCCT marker assessment seems to increase the prognostic accuracy for hematoma expansion in antithrombotic-related spontaneous ICH patients. Full article

(This article belongs to the Special Issue New Frontiers in the Clinical Management of Stroke)

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15 pages, 835 KiB

Open AccessArticle

Platelet-Derived Drug Targets and Biomarkers of Ischemic Stroke—The First Dynamic Human LC-MS Proteomic Study

by Karolina Gawryś, Aleksandra Turek-Jakubowska, Jakub Gawryś, Maciej Jakubowski, Janusz Dębski, Ewa Szahidewicz-Krupska, Małgorzata Trocha, Arkadiusz Derkacz and Adrian Doroszko

J. Clin. Med. 2022, 11(5), 1198; https://doi.org/10.3390/jcm11051198 - 23 Feb 2022

Cited by 4 | Viewed by 2738

Abstract

(1) Objective: The aim of this dynamic LC-MS (liquid chromatography and mass spectrometry) human platelet proteomic study was to identify the potential proteins candidates for biomarkers of acute ischemic stroke (AIS), their changes during the acute phase of stroke and to define potential novel drug targets. (2) Methods: A total of 32 patients (18–80 years old) were investigated that presented symptoms of AIS lasting less than 24 h from the onset, confirmed by neurological examination and/or new cerebral ischemia visualized in the CT (computed-tomography) scans. The analysis of platelet proteome was performed using LC-MS at baseline, and then on the third and seventh day from the onset of symptoms. The control group was demographically matched without any clinical signs of acute brain injury. (3) Results: The differences between platelets, at 24 h after first symptoms of stroke subjects and the control group included: β-amyloid A4 and amyloid-like protein 2, coactosin-like protein, thymidine phosphorylase 4 (TYMP-4), interferon regulatory factor 7 (IRF7), vitamin K-dependent protein S, histone proteins (H2A type 1 and 1-A, H2A types 2B and J, H2Av, -z, and -x), and platelet basic protein. The dynamic changes in the platelet protein concentration involved thrombospondin-1, thrombospondin-2, filamin A, B, and C. (4) Conclusions: This is the first human dynamic LC-MS proteomic study that differentiates platelet proteome in the acute phase of ischemic stroke in time series and compares the results with healthy controls. Identified proteins may be considered as future markers of ischemic stroke or therapeutic drug targets. Thymidine phosphorylase 4 (TYMP-4) holds promise as an interesting drug target in the management or prevention of ischemic stroke. Full article

(This article belongs to the Special Issue New Frontiers in the Clinical Management of Stroke)

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13 pages, 614 KiB

Open AccessArticle

New Candidates for Biomarkers and Drug Targets of Ischemic Stroke—A First Dynamic LC-MS Human Serum Proteomic Study

by Aleksandra Turek-Jakubowska, Janusz Dębski, Maciej Jakubowski, Ewa Szahidewicz-Krupska, Jakub Gawryś, Karolina Gawryś, Agnieszka Janus, Małgorzata Trocha and Adrian Doroszko

J. Clin. Med. 2022, 11(2), 339; https://doi.org/10.3390/jcm11020339 - 11 Jan 2022

Cited by 7 | Viewed by 3050

Abstract

(1) Background: The aim of this dynamic-LC/MS-human-serum-proteomic-study was to identify potential proteins-candidates for biomarkers of acute ischemic stroke, their changes during acute phase of stroke and to define potential novel drug-targets. (2) Methods: A total of 32 patients (29–80 years) with acute ischemic stroke were enrolled to the study. The control group constituted 29 demographically-matched volunteers. Subjects with stroke presented clinical symptoms lasting no longer than 24 h, confirmed by neurological-examination and/or new cerebral ischemia visualized in the CT scans (computed tomography). The analysis of plasma proteome was performed using LC-MS (liquid chromatography–mass spectrometry). (3) Results: Ten proteins with significantly different serum concentrations between groups volunteers were: complement-factor-B, apolipoprotein-A-I, fibronectin, alpha-2-HS-glycoprotein, alpha-1B-glycoprotein, heat-shock-cognate-71kDa protein/heat-shock-related-70kDa-protein-2, thymidine phosphorylase-2, cytoplasmic-tryptophan-tRNA-ligase, ficolin-2, beta-Ala-His-dipeptidase. (4) Conclusions: This is the first dynamic LC-MS study performed on a clinical model which differentiates serum proteome of patients in acute phase of ischemic stroke in time series and compares to control group. Listed proteins should be considered as risk factors, markers of ischemic stroke or potential therapeutic targets. Further clinical validation might define their exact role in differential diagnostics, monitoring the course of the ischemic stroke or specifying them as novel drug targets. Full article

(This article belongs to the Special Issue New Frontiers in the Clinical Management of Stroke)

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11 pages, 1233 KiB

Open AccessArticle

The Role of Factor Xa-Independent Pathway and Anticoagulant Therapies in Cancer-Related Stroke

by Hyung Jun Kim, Jong-Won Chung, Oh Young Bang, Yeon Hee Cho, Yun Jeong Lim, Jaechun Hwang, Woo-Keun Seo, Gyeong-Moon Kim, Hee-Jin Kim and Myung-Ju Ahn

J. Clin. Med. 2022, 11(1), 123; https://doi.org/10.3390/jcm11010123 - 27 Dec 2021

Cited by 7 | Viewed by 3185

Abstract

Background: The optimal strategy for stroke prevention in cancer patients is unknown. We compared the underlying mechanisms of coagulopathy and the effects of anticoagulants in patients with active cancer and atrial fibrillation (AF). Methods: We retrospectively enrolled 46 consecutive patients with embolic stroke of unknown source and active cancer (cancer stroke). We consecutively screened patients with cancer patients without stroke (n = 29), AF stroke (n = 52), and healthy subjects (n = 28), which served as controls. Patients with cancer stroke were treated with either enoxaparin (a low-molecular-weight heparin) or a factor Xa inhibitor, and those with AF stroke were treated with factor Xa inhibitors. D-dimer, factor Xa, and circulating cell-free DNA (cfDNA), a marker of neutrophil extracellular traposis, were measured at both before and after anticoagulation. Results: In AF stroke, factor Xa activity and cfDNA and D-dimer levels were decreased by treatment with factor Xa inhibitors. In contrast, in cancer stroke, factor Xa activity was decreased, D-dimer levels were unchanged, and cfDNA levels were increased by treatment with factor Xa inhibitors. In cancer stroke patients treated with enoxaparin, D-dimer levels were decreased (p = 0.011) and cfDNA levels were unchanged. Conclusion: The anticoagulation effects of factor Xa inhibitors differed between cancer stroke and AF stroke. Full article

(This article belongs to the Special Issue New Frontiers in the Clinical Management of Stroke)

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Review

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17 pages, 4590 KiB

Open AccessReview

Acute Onset Quadriplegia and Stroke: Look at the Brainstem, Look at the Midline

by Marialuisa Zedde, Ilaria Grisendi, Francesca Romana Pezzella, Manuela Napoli, Claudio Moratti, Franco Valzania and Rosario Pascarella

J. Clin. Med. 2022, 11(23), 7205; https://doi.org/10.3390/jcm11237205 - 4 Dec 2022

Cited by 3 | Viewed by 5222

Abstract

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. Full article

(This article belongs to the Special Issue New Frontiers in the Clinical Management of Stroke)

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12 pages, 1866 KiB

Open AccessReview

Mechanisms and Neuroimaging Patterns of Hypereosinophilia-Related Ischemic Stroke: A Narrative Review through Three Cases

by Maria Cristina Cioclu, Francesco Cavallieri, Manuela Napoli, Claudio Moratti, Rosario Pascarella, Franco Valzania and Marialuisa Zedde

J. Clin. Med. 2022, 11(19), 5595; https://doi.org/10.3390/jcm11195595 - 23 Sep 2022

Cited by 3 | Viewed by 3891

Abstract

Background: Hypereosinophilic syndromes (HES) are a group of relatively rare disorders in which neurological manifestations, including ischemic stroke, are common. The hypothesized pathophysiological mechanisms are hypercoagulability, cardioembolism (mainly mediated by myocardial involvement) and damage to the endothelium. A variable ischemic pattern has been described, including an association of territorial and border zone ischemic stroke. Methods: Three patients who presented to our department with acute stroke were selected aiming to show these three different mechanisms inferred from the stroke pattern on brain Magnetic Resonance Imaging (MRI) and to simultaneously illustrate the three main causes of HES. Results and Discussion: The first patient is a 55-year-old man with an abrupt onset of aphasia due to an acute ischemic stroke involving the left parietal lobule and the angular gyrus; recent lab test had shown hypereosinophilia. An extensive workup excluded primary and secondary causes of hypereosinophilia so a diagnosis of idiopathic hypereosinophilia was done and he was treated with high doses of steroids. The second patient had severe hypereosinophilia and developed multiple small, scattered ischemic lesions, mainly in border zone zones. The history of severe asthma and recurrent sinusitis supported the diagnosis of EGPA (Eosinophilic Granulomatosis with Polyangiitis); considering the severe clinical conditions and the presumptive role of hypereosinophilia in determining her symptoms, steroid treatment was promptly started, with good clinical response. The third patient also presented with multiple metachronous ischemic lesions, both in cortical and border zone distribution and marked eosinophilia; the diagnostic work-up found an ovarian cancer. She was treated with steroids and then underwent surgery and adjuvant chemotherapy. Conclusions: HES should be considered in stroke etiological evaluation, although it is a rare disorder, and border zones pattern without large artery steno-occlusion on neuroimaging may help to raise the suspicion in the neurovascular diagnostic pathway. A thorough research of the sources of hypereosinophilia should be performed to select the appropriate therapy. Full article

(This article belongs to the Special Issue New Frontiers in the Clinical Management of Stroke)

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19 pages, 1356 KiB

Open AccessReview

Forgetting the Unforgettable: Transient Global Amnesia Part II: A Clinical Road Map

by Marco Sparaco, Rosario Pascarella, Carmine Franco Muccio and Marialuisa Zedde

J. Clin. Med. 2022, 11(14), 3940; https://doi.org/10.3390/jcm11143940 - 6 Jul 2022

Cited by 8 | Viewed by 6269

Abstract

Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of a temporary memory disorder with profound anterograde amnesia and a variable impairment of the past memory. Usually, the attacks are preceded by a precipitating event, last up to 24 h and are not associated with other neurological deficits. Diagnosis can be challenging because the identification of TGA requires the exclusion of some acute amnestic syndromes that occur in emergency situations and share structural or functional alterations of memory circuits. Magnetic Resonance Imaging (MRI) studies performed 24–96 h after symptom onset can help to confirm the diagnosis by identifying lesions in the CA1 field of the hippocampal cornu ammonis, but their practical utility in changing the management of patients is a matter of discussion. In this review, we aim to provide a practical approach to early recognition of this condition in daily practice, highlighting both the lights and the shadows of the diagnostic criteria. For this purpose, we summarize current knowledge about the clinical presentation, diagnostic pathways, differential diagnosis, and the expected long-term outcome of TGA. Full article

(This article belongs to the Special Issue New Frontiers in the Clinical Management of Stroke)

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13 pages, 854 KiB

Open AccessReview

Forgetting the Unforgettable: Transient Global Amnesia Part I: Pathophysiology and Etiology

by Marco Sparaco, Rosario Pascarella, Carmine Franco Muccio and Marialuisa Zedde

J. Clin. Med. 2022, 11(12), 3373; https://doi.org/10.3390/jcm11123373 - 12 Jun 2022

Cited by 12 | Viewed by 5133

Abstract

Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of a temporary memory disorder with a profound anterograde amnesia and a variable impairment of the past memory. Since the first description, dating back over 60 years, several cases have beenreported in the literature. Nevertheless, TGA remains one of the most mysterious diseases in clinical neurology. The debate regarding the etiology of this disease has focused mainly on three different mechanisms: vascular (due to venous flow changes or focal arterial ischemia), epileptic, and migraine related. However, to date there is no scientific proof of any of these mechanisms. Furthermore, the demonstration by diffusion-weighted MRI of lesions in the CA1 field of the hippocampus cornu ammonis led us to hypothesize that the selective vulnerability of CA1 neurons to metabolic stress could play a role in the pathophysiology of TGA. In this review, we summarize current knowledge on the anatomy, vascularization and function of the hippocampus. Furthermore, we discuss the emerging theories on the etiology and the pathophysiological cascade leading to an impairment of hippocampal function during the attacks. Full article

(This article belongs to the Special Issue New Frontiers in the Clinical Management of Stroke)

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Other

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14 pages, 3864 KiB

Open AccessCase Report

Neurovascular Manifestations of Iron-Deficient Anemia: Narrative Review and Practical Reflections through a Teaching Case

by Marialuisa Zedde, Giacomo Portaro, Laura Ferri, Francesco Cavallieri, Manuela Napoli, Claudio Moratti, Fabrizio Piazza, Franco Valzania and Rosario Pascarella

J. Clin. Med. 2022, 11(20), 6088; https://doi.org/10.3390/jcm11206088 - 15 Oct 2022

Viewed by 2510

Abstract

Anemia is one of the most frequent diseases worldwide, affecting one-third of the general population. Anemia in general and in particular, iron-deficient anemia (IDA), has been associated to a higher risk of thrombotic manifestations, including ischemic stroke and cerebral venous thrombosis (CVT), as well as systemic extra-cerebral arterial and venous thrombosis. Despite these data, anemia is seldom considered as an etiological factor of stroke. An individual case encompassing all known neurovascular and systemic arterial and venous thrombotic manifestations related to IDA is presented with the focus on clinical reasoning issues in the diagnostic pathways, starting from the neuroradiological signs. The main questions have been identified and addressed in a narrative review of the most relevant data in the literature from a pragmatic and clinical viewpoint. The presented case concerns a 46-year-old man admitted to the Stroke Unit because of acute ischemic stroke with multiple thrombi in large intracranial and extracranial vessels, multifocal ischemic lesions in several arterial territories and the concurrent finding of asymptomatic CVT, pulmonary embolism with lung infarction and aortic thrombosis. An extended diagnostic work-up excluded the main etiologies (arterial dissection, cardiac embolism, genetic and acquired prothrombotic disorders, such as cancer and antiphospholipid syndrome), except for a severe IDA, such as to require blood transfusions followed by anticoagulant therapy for the several thrombotic manifestations. Neuroimaging and systemic vascular findings have been analyzed, and the main issues proposed by the case in the diagnostic pathway have been identified and discussed in a pragmatic clinical road map reviewing the data provided by the literature. Conclusions: IDA is a common but treatable condition that, independently or synergically, may increase the risk of thrombotic events. The diagnostic and therapeutic approach has not yet been defined, and each case should be individually addressed in a pragmatic clinical road map. Full article

(This article belongs to the Special Issue New Frontiers in the Clinical Management of Stroke)

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