Bridging the Gap: Harnessing Plant Bioactive Molecules to Target Gut Microbiome Dysfunctions in Amyotrophic Lateral Sclerosis.

The correlation between neurodegenerative diseases and the gut microbiome is increasingly evident, with amyotrophic lateral sclerosis (ALS) being particularly notable for its severity and lack of therapeutic options. The gut microbiota, implicated in the pathogenesis and development of ALS, plays a crucial role in the disease. Bioactive plant molecules, specifically volatile compounds in essential oils, offer a promising therapeutic avenue due to their anti-inflammatory properties and gut-modulating effects. Our narrative review aimed to identify microbiota-associated bacteria in ALS and analyze the benefits of administering bioactive plant molecules as much-needed therapeutic options in the management of this disease. A comprehensive search of PubMed database articles published before December 2023, encompassing research on cell, human, and animal ALS models, was conducted. After selecting, analyzing, and discussing key articles, bacteria linked to ALS pathogenesis and physiopathology were identified. Notably, positively highlighted bacteria included Akkermansia muciniphila (Verrucomicrobia phylum), Faecalibacterium prausnitzii, and Butyrivibrio spp. (Firmicutes phylum). Conversely, members of the Escherichia coli spp. (Proteobacteria phylum) and Ruminococcus spp. (Firmicutes phylum) stood out negatively in respect to ALS development. These bacteria were associated with molecular changes linked to ALS pathogenesis and evolution. Bioactive plant molecules can be directly associated with improvements in the microbiome, due to their role in reducing inflammation and oxidative stress, emerging as one of the most promising natural agents for enriching present-day ALS treatments.

Exploring the Role of Metabolic Hormones in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive loss of motor neurons. Emerging evidence suggests a potential link between metabolic dysregulation and ALS pathogenesis. This study aimed to investigate the relationship between metabolic hormones and disease progression in ALS patients. A cross-sectional study was conducted involving 44 ALS patients recruited from a tertiary care center. Serum levels of insulin, total amylin, C-peptide, active ghrelin, GIP (gastric inhibitory peptide), GLP-1 active (glucagon-like peptide-1), glucagon, PYY (peptide YY), PP (pancreatic polypeptide), leptin, interleukin-6, MCP-1 (monocyte chemoattractant protein-1), and TNFα (tumor necrosis factor alpha) were measured, and correlations with ALSFRS-R, evolution scores, and biomarkers were analyzed using Spearman correlation coefficients. Subgroup analyses based on ALS subtypes, progression pattern of disease, and disease progression rate patterns were performed. Significant correlations were observed between metabolic hormones and ALS evolution scores. Insulin and amylin exhibited strong correlations with disease progression and clinical functional outcomes, with insulin showing particularly robust associations. Other hormones such as C-peptide, leptin, and GLP-1 also showed correlations with ALS progression and functional status. Subgroup analyses revealed differences in hormone levels based on sex and disease evolution patterns, with male patients showing higher amylin and glucagon levels. ALS patients with slower disease progression exhibited elevated levels of amylin and insulin. Our findings suggest a potential role for metabolic hormones in modulating ALS progression and functional outcomes. Further research is needed to elucidate the underlying mechanisms and explore the therapeutic implications of targeting metabolic pathways in ALS management.

A Potential Role of Interleukin-5 in the Pathogenesis and Progression of Amyotrophic Lateral Sclerosis: A New Molecular Perspective.

Cumulative data suggest that neuroinflammation plays a prominent role in amyotrophic lateral sclerosis (ALS) pathogenesis. The purpose of this work was to assess if patients with ALS present a specific peripheral cytokine profile and if it correlates with neurological disability assessed by ALSFRS-R, the rate of disease progression, and the pattern of disease progression (horizontal spreading [HSP] versus vertical spreading [VSP]). We determined the levels of 15 cytokines in the blood of 59 patients with ALS and 40 controls. We identified a positive correlation between levels of pro-inflammatory cytokines (interleukin [IL]-17F, IL-33, IL-31) and the age of ALS patients, as well as a positive correlation between IL-12p/70 and survival from ALS onset and ALS diagnosis. Additionally, there was a positive correlation between the ALSFRS-R score in the upper limb and respiratory domain and IL-5 levels. In our ALS cohort, the spreading pattern was 42% horizontal and 58% vertical, with patients with VSP showing a faster rate of ALS progression. Furthermore, we identified a negative correlation between IL-5 levels and the rate of disease progression, as well as a positive correlation between IL-5 and HSP of ALS. To the best of our knowledge, this is the first study reporting a "protective" role of IL-5 in ALS.

Characteristics of Developmental and Epileptic Encephalopathy Associated with PACS2 p.Glu209Lys Pathogenic Variant-Our Experience and Systematic Review of the Literature.

BACKGROUND: Developmental and epileptic encephalopathies (DEE) encompass a group of rare diseases with hereditary and genetic causes as well as acquired causes such as brain injuries or metabolic abnormalities. The phosphofurin acidic cluster sorting protein 2 (PACS2) is a multifunctional protein with nuclear gene expression. The first cases of the recurrent c.625G>A pathogenic variant of PACS2 gene were reported in 2018 by Olson et al. Since then, several case reports and case series have been published. METHODS: We performed a systematic review of the PUBMED and SCOPUS databases using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Our search parameters included DEE66 with a pathogenic PACS2 gene p.Glu209Lys mutation published cases to which we added our own clinical experience regarding this pathology. RESULTS: A total of 11 articles and 29 patients were included in this review, to which we added our own experience for a total of 30 patients. There was not a significant difference between sexes regarding the incidence of this pathology (M/F: 16/14). The most common neurological and psychiatric symptoms presented by the patients were: early onset epileptic seizures, delayed global development (including motor and speech delays), behavioral disturbances, limited intellectual capacity, nystagmus, hypotonia, and a wide-based gait. Facial dysmorphism and other organs' involvement were also frequently reported. Brain MRIs evidenced anomalies of the posterior cerebellar fossa, foliar distortion of the cerebellum, vermis hypoplasia, white matter reduction, and lateral ventricles enlargement. Genetic testing is more frequent in children. Only 4 cases have been reported in adults to date. CONCLUSIONS: It is important to maintain a high suspicion of new pathogenic gene variants in adult patients presenting with a characteristic clinical picture correlated with radiologic changes. The neurologist must gradually recognize the distinct evolving phenotype of DEE66 in adult patients, and genetic testing must become a scenario with which the neurologist attending adult patients should be familiar. Accurate diagnosis is required for adequate treatment, genetic counseling, and an improved long-term prognosis.

The Role of Short-Chain Fatty Acids in Microbiota-Gut-Brain Cross-Talk with a Focus on Amyotrophic Lateral Sclerosis: A Systematic Review.

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease characterized by the gradual loss of motor neurons in the brain and spinal cord, leading to progressive motor function decline. Unfortunately, there is no effective treatment, and its increasing prevalence is linked to an aging population, improved diagnostics, heightened awareness, and changing lifestyles. In the gastrointestinal system, the gut microbiota plays a vital role in producing metabolites, neurotransmitters, and immune molecules. Short-chain fatty acids, of interest for their potential health benefits, are influenced by a fiber- and plant-based diet, promoting a diverse and balanced gut microbiome. These fatty acids impact the body by binding to receptors on enteroendocrine cells, influencing hormones like glucagon-like peptide-1 and peptide YY, which regulate appetite and insulin sensitivity. Furthermore, these fatty acids impact the blood-brain barrier, neurotransmitter levels, and neurotrophic factors, and directly stimulate vagal afferent nerves, affecting gut-brain communication. The vagus nerve is a crucial link between the gut and the brain, transmitting signals related to appetite, inflammation, and various processes. Dysregulation of this pathway can contribute to conditions like obesity and irritable bowel syndrome. Emerging evidence suggests the complex interplay among these fatty acids, the gut microbiota, and environmental factors influences neurodegenerative processes via interconnected pathways, including immune function, anti-inflammation, gut barrier, and energy metabolism. Embracing a balanced, fiber-rich diet may foster a diverse gut microbiome, potentially impacting neurodegenerative disease risk. Comprehensive understanding requires further research into interventions targeting the gut microbiome and fatty acid production and their potential therapeutic role in neurodegeneration.

The peripheral profile of the chitinase 3-like-1 in benign multiple sclerosis - a single centre's experience.

BACKGROUND: A limited subgroup of multiple sclerosis (MS) patients present with a long-term disease evolution characterized by a limited disease progression, known as benign MS (BMS). Chitinase 3-like-1 (CHI3L1) levels are sensitive to inflammatory processes and may play a role in the pathogenesis of MS. In this observational, cross-sectional study, we aimed to evaluate the implications of serum CHI3L1 and inflammatory cytokines in BMS patients treated with interferon ß-1b for over a decade. METHODS: We collected serum samples from 17 BMS patients and 17 healthy controls (HC) to measure serum CHI3L1 levels and a Th17 panel of inflammatory cytokines. Serum levels of CHI3L1 were analysed using the sandwich ELISA method and the Th17 panel was assessed using the multiplex XMap technology on a Flexmap 3D Analyzer. RESULTS: Serum CHI3L1 levels did not differ significantly from HC. We identified a positive correlation between CHI3L1 levels and relapses during treatment. CONCLUSIONS: Our findings suggest that there are no differences in serum CHI3L1 levels between BMS patients and HC. However, serum CHI3L1 levels are sensitive to clinical inflammatory activity and may be associated with relapses in BMS patients.

Recent Progress in the Identification of Early Transition Biomarkers from Relapsing-Remitting to Progressive Multiple Sclerosis.

Despite extensive research into the pathophysiology of multiple sclerosis (MS) and recent developments in potent disease-modifying therapies (DMTs), two-thirds of relapsing-remitting MS patients transition to progressive MS (PMS). The main pathogenic mechanism in PMS is represented not by inflammation but by neurodegeneration, which leads to irreversible neurological disability. For this reason, this transition represents a critical factor for the long-term prognosis. Currently, the diagnosis of PMS can only be established retrospectively based on the progressive worsening of the disability over a period of at least 6 months. In some cases, the diagnosis of PMS is delayed for up to 3 years. With the approval of highly effective DMTs, some with proven effects on neurodegeneration, there is an urgent need for reliable biomarkers to identify this transition phase early and to select patients at a high risk of conversion to PMS. The purpose of this review is to discuss the progress made in the last decade in an attempt to find such a biomarker in the molecular field (serum and cerebrospinal fluid) between the magnetic resonance imaging parameters and optical coherence tomography measures.

Serum Fatty Acids Are Associated with a Higher Risk of Ischemic Stroke.

Stroke prevention, a significant public-health concern, begins with recognizing and addressing risk factors. Interventions targeted at modifiable risk factors can effectively prevent ischemic stroke, while Omega-3 fatty acids have been shown to improve stroke outcomes. Our study aimed to investigate the relationship between ischemic-stroke risk factors and fatty acids using a prospective observational study with 274 patients. We collected clinical data on risk factors and measured fatty-acid levels using high-performance liquid chromatography coupled with mass spectrometry. We found that several risk factors, including age, sex, smoking, atrial fibrillation, dyslipidemia, and previous stroke history, had a direct relationship with fatty acids. Of these, smoking had the most significant impact, negatively impacting levels of docosahexaenoic and eicosapentaenoic acid. Conversely, dyslipidemia and atrial fibrillation positively correlated with fatty acids, particularly in female patients and those with recurrent strokes. Age was found to directly correlate with other risk factors and variations in fatty-acid ratios. The stroke rate was higher in males than females before the age of 70, but this trend reversed. Our findings suggest that better management of risk factors, particularly modifiable lifestyle factors, could improve fatty-acid profiles and the balance of Omega-3 and Omega-6 in patients with ischemic stroke.

Cytokine Secretion Dynamics of Isolated PBMC after Cladribine Exposure in RRMS Patients.

Cladribine (CLD) treats multiple sclerosis (MS) by selectively and transiently depleting B and T cells with a secondary long-term reconstruction of the immune system. This study provides evidence of CLD's immunomodulatory role in peripheral blood mononuclear cells (PBMCs) harvested from 40 patients with untreated relapsing-remitting MS (RRMS) exposed to CLD. We quantified cytokine secretion from PBMCs isolated by density gradient centrifugation with Ficoll−Paque using xMAP technology on a FlexMap 3D analyzer with a highly sensitive multiplex immunoassay kit. The PBMC secretory profile was evaluated with and without CLD exposure. PBMCs isolated from patients with RRMS for ≤12 months had significantly higher IL-4 but significantly lower IFN-γ and TNF-α secretion after CLD exposure. PBMCs isolated from patients with RRMS for >12 months had altered inflammatory ratios toward an anti-inflammatory profile and increased IL-4 but decreased TNF-α secretion after CLD exposure. CLD induced nonsignificant changes in IL-17 secretion in both RRMS groups. Our findings reaffirm CLD's immunomodulatory effect that induces an anti-inflammatory phenotype.

Fatty Acids and Lipid Paradox-Neuroprotective Biomarkers in Ischemic Stroke.

Stroke is the primary cause of death and disability worldwide, with ischemic stroke up to 80% of the total cases. Lipid profile was established as a major risk factor for stroke, but recent studies show a paradoxical relationship between serum values and the outcome of stroke patients. Our study aims to analyze the impact of the classic extended lipid profile, including fatty acids as potential neuroprotective biomarkers for the outcome of ischemic stroke patients. We included 298 patients and collected clinical, paraclinical, and outcome parameters. We used a method consisting of high-performance liquid chromatography coupled with mass spectrometry to quantify serum fatty acids. We observed a negative correlation between National Institutes of Health Stroke Scale (NIHSS) at admission and total cholesterol (p = 0.040; r = -0.120), respectively triglycerides (p = 0.041; r = -0.122). The eicosapentaenoic to arachidonic acid ratio has a negative correlation, while the docosahexaenoic to eicosapentaenoic acid ratio positively correlates with all the prognostic parameters, showing a potential neuroprotective role for eicosapentaenoic acid in preventing severe ischemic stroke. The impact of the lipid profile paradox and the dependency relationship with the fatty acids represent a significant predictive factor for the functional and disability prognostic of ischemic stroke patients.

Autoimmune Encephalitis in COVID-19 Infection: Our Experience and Systematic Review of the Literature.

The neurologic complications of COVID-19 infection are frequent in hospitalized patients; a high percentage of them present neurologic manifestations at some point during the course of their disease. Headache, muscle pain, encephalopathy and dizziness are among the most common complications. Encephalitis is an inflammatory condition with many etiologies. There are several forms of encephalitis associated with antibodies against intracellular neuronal proteins, cell surfaces or synaptic proteins, referred to as autoimmune encephalitis. Several case reports published in the literature document autoimmune encephalitis cases triggered by COVID-19 infection. Our paper first presents our experience in this issue and then systematically reviews the literature on autoimmune encephalitis that developed in the background of SARS-CoV-2 infections and also discusses the possible pathophysiological mechanisms of auto-immune-mediated damage to the nervous system. This review contributes to improve the management and prognosis of COVID-19-related autoimmune encephalitis.

Neuroprotection in Stroke-Focus on the Renin-Angiotensin System: A Systematic Review.

Stroke is the primary cause of disability in the adult population. Hypertension represents the leading risk factor being present in almost half the patients. The renin-angiotensin system is involved in the physiopathology of stroke and has an essential impact on hypertension as a risk factor. This article targeted the role of the renin-angiotensin system in stroke neuroprotection by reviewing the current literature available. The mechanism of action of the renin-angiotensin system was observed through the effects on AT1, AT2, and Mas receptors. The neuroprotective properties ascertained by angiotensin in stroke seem to be independent of the blood pressure reduction mechanism, and include neuroregeneration, angiogenesis, and increased neuronal resistance to hypoxia. The future relationship of stroke and the renin-angiotensin system is full of possibilities, as new agonist molecules emerge as potential candidates to restrict the impairment caused by stroke.

In-House Validated Map of Lymph Node Stations in a Prospective Cohort of Colorectal Cancer: A Tool for a Better Preoperative Staging.

Preoperative staging of colorectal cancer (CRC) based on imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) is crucial for identification and then removal of the positive lymph nodes (LNs). The aim of this study was to evaluate the correlation between preoperatively seen morphologic criteria (number, size, shape, structure, borders, or enhancement patterns) and histopathological features of LNs using an in-house validated map of nodal stations. A total of 112 patients with CRC that underwent surgery were preoperatively evaluated by CT scans. The locoregional, intermediate, and central LNs were CT-mapped and then removed during open laparotomy and examined under microscope. The analysis of correlations was interpreted using the suspicious-to-positive ratio (SPR) parameter. The greatest correlation was found in tumors located in the sigmoid colon, descending colon and middle rectum; SPR value was 1.12, 1.18, and 1.26, respectively. SPR proved to be 0.59 for cases of the transverse colon. Regarding the enhancement type, the dotted pattern was mostly correlated with metastatic LNs (OR: 7.84; p < 0.0001), while the homogenous pattern proved a reliable indicator of nonmetastatic LNs (OR: 1.99; p < 0.05). A total of 1809 LNs were harvested, with a median value of 15 ± 1.34 LNs/case. Transdisciplinary approach of CRC focused on pre-, intra-, and postoperatively mapping of LNs might increase the accuracy of detecting metastasized nodes for tumors of the distal colon and middle rectum but not for those of the transverse colon. In addition to morphologic criteria, the enhancement pattern of LNs can be used as a predictor of nodal involvement improving the CT-based preoperative staging.

Rivaroxaban for the treatment of cerebral venous thrombosis: a single-center experience.

The mainstay of cerebral venous thrombosis (CVT) treatment according to current guidelines is parenteral anticoagulation with unfractionated heparin or low-molecular-weight heparin followed by long-term oral anticoagulation with vitamin K antagonists. Direct oral anticoagulants (DOACs), including the factor Xa inhibitor rivaroxaban, are used occasionally off-label for CVT based on individual treatment plans. This publication sought to report our experience with rivaroxaban for the indication of CVT and to review the relevant literature data concerning this topic. We performed a single-center retrospective analysis including patients from our institution with the diagnosis of cerebral venous thrombosis treated with rivaroxaban. Among 12,500 stroke patients over an 11-year period, we identified 87 cases with a diagnosis of CVT (0.7%). As long-term anticoagulation, 80 of these patients were receiving vitamin K antagonists and seven were receiving DOACs, including six receiving rivaroxaban and one receiving apixaban. Of the six patients receiving rivaroxaban, at least 6 months of clinical follow-up data were available for five of them. Excellent clinical outcomes were obtained in four of these five cases (modified Rankin scale score: 0-1 points). No hemorrhagic events, recurrent thrombosis, or other relevant complications were recorded during the follow-up period. Despite our small study sample size, our positive results support that rivaroxaban may be a safe and effective treatment option for patients with CVT. Hopefully, ongoing randomized clinical trials will better clarify the role of rivaroxaban in the treatment of CVT so as to provide a more convenient and safer alternative to vitamin K antagonists in this context.

Prevalence and Clinical Characteristics of Subclavian Steal Phenomenon/Syndrome in Patients with Acute Ischemic Stroke.

There are no published clinical studies regarding the prevalence of subclavian steal among acute ischemic stroke patients. The aim of this study was to evaluate the prevalence and clinical significance of subclavian steal among a large number of consecutive ischemic stroke patients. MATERIALS AND METHODS: We reviewed the medical records of 2192 consecutive cases of acute ischemic stroke at a tertiary neurology clinic in Targu Mures, Romania, between 2018 and 2020. In total, 47 patients (2.2%) were diagnosed with subclavian steal phenomenon/syndrome. RESULTS: Stroke patients with associated steal phenomenon were significantly younger (64.2 ± 11.1 versus 70.2 ± 12.8, p = 0.005) and predominantly male (68.1%). From among the 47 patients with subclavian steal phenomenon, nine (19.1%) presented stroke symptomatology in the vertebrobasilar territory. Overall, 83.3% of the stroke patients with associated steal phenomenon presented cerebral infarction and 16.7% presented TIA. There was no difference between groups regarding the affected vascular territory (VB versus carotid). Large artery atherosclerosis was more frequent in the stroke group with associated steal phenomenon (81.3% versus 43.5%, p = 0.0033). The NIHSS score at admission was higher in the patient group with associated steal phenomenon, but there was no difference in mRS at discharge. Associated carotid artery occlusion was more frequent in the stroke group with steal phenomenon (p < 0.01). Smoking and peripheral arteriopathy were more frequent in the patient group with associated steal phenomenon. Of the nine symptomatic patients, five underwent revascularization treatment. CONCLUSIONS: The prevalence of subclavian steal phenomenon among acute ischemic stroke patients was not higher than in other cohorts with heterogenous peripheral vascular pathologies. Similar to the general population, in acute ischemic stroke patients, the associated subclavian steal behaved like a benign hemodynamical condition, without severe consequences.

Ischemic Stroke in Patients with Cancer: a Retrospective Cross-Sectional Study.

INTRODUCTION: An increasing trend of cancer associated stroke has been noticed in the past decade. OBJECTIVES: To evaluate the risk factors and the incidence of neoplasia in stroke patients. MATERIAL AND METHOD: A retrospective, observational study was undertaken on 249 patients with stroke and active cancer (SAC) and 1563 patients with stroke without cancer (SWC). The general cardiovascular risk factors, the site of cancer, and the general clinical data were registered and evaluated. According to the "Oxfordshire Community Stroke Project" (OCSP) classification, all patients were classified into the clinical subtypes of stroke. The aetiology of stroke was considered as large-artery atherosclerosis, small vessel disease, cardio-embolic, cryptogenic or other determined cause. RESULTS: The severity of neurological deficits at admission were significantly higher in the SAC group (p<0.01). The haemoglobin level was significantly lower, and platelet level and erythrocyte sedimentation rate were significantly higher in the SAC group. Glycaemia, cholesterol and triglycerides levels were significantly higher in the SWC group. The personal history of hypertension was more frequent in the SWC group. In the SAC group, 28.9% had a cryptogenic aetiology, compared to 9.1% in SWC group. Cardio-embolic strokes were more frequent in the SAC group (24%) than the SWC group (19.6%). In the SAC group, 15,6% were diagnosed with cancer during the stroke hospitalization, and 78% of the SAC patients were without metastasis. CONCLUSIONS: The most frequent aetiologies of stroke in cancer patients were cryptogenic stroke, followed by large-artery atherosclerosis. SAC patients had more severe neurological deficits and worse clinical outcomes than SWC patients. Stroke in cancer patients appears to be more frequently cryptogenic, probably due to cancer associated thrombosis. The association between stroke and cancer is important, especially in stroke of cryptogenic mechanism, even in the presence of traditional cardiovascular risk factors.

Contrast Medium-Induced Encephalopathy After Coronary Angiography- Case Report.

INTRODUCTION: Contrast-induced encephalopathy represents a rare, reversible complication that appears after intravenous or intra-arterial exposure to contrast agents. There is no consensus in the literature regarding the mechanism of action. However, the theoretical mechanism is set around the disruption of the blood-brain barrier and the contrast agents' chemical properties. CASE REPORT: The case of a 70-year-old patient, known to have hypertension and type 2 diabetes mellitus is reported. The patient had undergone a diagnostic coronary angiography during which he received 100ml of Ioversol (Optiray 350™). Soon after the procedure, the patient began experiencing a throbbing headache, followed by intense behavioural changes and aggressive tendencies. He was transferred to the Neurology Clinic. The neurological examination was without focal neurological signs; however, the patient was very aggressive and uncooperative. The CT scan revealed a mild hyper-density in the frontal lobes. MRI scan revealed no pathological changes. Conservative treatment with diuretics and hydration was administered, and the patient experienced a complete resolution of symptoms in 72 hours. CONCLUSION: Contrast-induced encephalopathy is a possible secondary complication to contrast agents and a diagnostic challenge, and it should not be overlooked, especially following procedures that use contrast agents.

The Role of Biomarkers in Atherothrombotic Stroke-A Systematic Review.

Stroke represents the primary debilitating disease in adults and is the second-highest cause of death worldwide. Atherosclerosis, the most prevalent etiology for vascular conditions, is a continuous process that gradually creates and develops endothelial lesions known as atherosclerotic plaques. These lesions lead to the appearance of atherothrombotic stroke. In the last decades, the role of biological biomarkers has emerged as either diagnostic, prognostic, or therapeutic targets. This article aims to create a list of potential biomarkers related to atherothrombotic stroke by reviewing the currently available literature. We identified 23 biomarkers and assessed their roles as risk factors, detection markers, prognostic predictors, and therapeutic targets. The central aspect of these biomarkers is related to risk stratification, especially for patients who have not yet suffered a stroke. Other valuable data are focused on the predictive capabilities for stroke patients regarding short-term and long-term prognosis, including their influence over the acute phase treatment, such as rt-PA thrombolysis. Although the role of biomarkers is anticipated to be of extreme value in the future, they cannot yet compete with traditional stroke neuroimaging markers but could be used as additional tools for etiological diagnosis.

Guillain-Barré syndrome associated with Covid-19: A close relationship or just a coincidence? (Review).

Several neurological complications affecting the central and peripheral nervous system were described secondary to COVID-19 infection such as hyposmia, headache, nausea, impaired consciousness, psychosis, neurocognitive syndromes and even cerebrovascular accidents. The mechanism of these complications is not fully understood, but heterogenous mechanisms such as cytokine storm, secondary hypercoagulability and direct neurotropism of the virus are thought to be involved. Guillain-Barré syndrome is a heterogeneous disease that frequently follows a bacterial or viral infection. During the ongoing SARS-CoV-2 pandemic, several isolated case reports and case series have suggested an association between this viral infection and the occurrence of Guillain-Barré syndrome. The main mechanism of Guillain-Barré syndrome is probably post-viral dysregulation of the immune system generated by SARS-CoV-2. The clinical characteristics and disease evolution seem to be similar to those observed in Guillain-Barré syndrome secondary to other etiologies. The aim of the present review is to summarize the relevant literature regarding SARS-CoV-2-related Guillain-Barré syndrome.

Stroke secondary to giant-cell arteritis: A literature review.

Stroke is a leading cause of death and disability worldwide. In addition to the classical etiologies of stroke as atherosclerosis and cardioembolism there are many unusual, rare causes, which require a high level of clinical suspicion and further investigations for correct and early diagnosis and adequate treatment. Giant-cell arteritis or temporal arteritis, the most frequent vasculitis in the elderly population is one of the uncommon causes of stroke. In the setting of giant-cell arteritis, stroke more likely affects the vertebrobasilar territory and is the main cause of mortality. Duplex ultrasound examination is a routine investigation for stroke patients and may be key to the diagnosis if the classical hypoechoic 'halo sign' is recognized at the level of vertebral arteries. In this situation the ultrasound evaluation of temporal arteries and temporal artery biopsy are mandatory. The Giant-cell arteritis-related stroke is a rare condition; therefore, there are no evidence-based guidelines or standard recommendations for the treatment. In the present review, the main characteristics of giant-cell arteritis-related stroke are discussed.