Performance of Different Risk Scores for the Detection of Atrial Fibrillation Among Patients With Cryptogenic Stroke.

BACKGROUND: Atrial fibrillation (AF) is a frequent underlying cause of cryptogenic stroke (CS) and its detection can be increased using implantable cardiac monitoring (ICM). We sought to evaluate different risk scores and assess their diagnostic ability in identifying patients with CS with underlying AF on ICM. METHODS: Patients with CS, being admitted to a single tertiary stroke center between 2017 and 2022 and receiving ICM, were prospectively evaluated. The CHA2DS2-VASc, HAVOC, Brown ESUS-AF, and C2HEST scores were calculated at baseline. The primary outcome of interest was the detection of AF, which was defined as at least 1 AF episode on ICM lasting for 2 consecutive minutes or more. The diagnostic accuracy measures and the net reclassification improvement were calculated for the 4 risk scores. Stroke recurrence was evaluated as a secondary outcome. RESULTS: A total of 250 patients with CS were included, and AF was detected by ICM in 20.4% (n=51) during a median monitoring period of 16 months. Patients with CS with AF detection were older compared with the rest (P=0.045). The median HAVOC, Brown ESUS-AF, and C2HEST scores were higher among the patients with AF compared with the patients without AF (all P<0.05), while the median CHA2DS2-VASc score was similar between the 2 groups. The corresponding C statistics for CHA2DS2-VASc, HAVOC, Brown ESUS-AF, and C2HEST for AF prediction were 0.576 (95% CI, 0.482-0.670), 0.612 (95% CI, 0.523-0.700), 0.666 (95% CI, 0.587-0.746), and 0.770 (95% CI, 0.699-0.839). The C2HEST score presented the highest diagnostic performance based on C statistics (P<0.05 after correction for multiple comparisons) and provided significant improvement in net reclassification for AF detection (>70%) compared with the other risk scores. Finally, stroke recurrence was documented in 5.6% of the study population, with no difference regarding the 4 risk scores between patients with and without recurrent stroke. CONCLUSIONS: The C2HEST score was superior to the CHA2DS2-VASc, HAVOC, and Brown ESUS-AF scores for discriminating patients with CS with underlying AF using ICM.

Icatibant averting mechanical ventilation in acute ischemic stroke patient with alteplase-induced orolingual angioedema.

BACKGROUND AND PURPOSE: Orolingual angioedema (OA) represents a rare but life-threatening complication among patients with acute ischemic stroke treated with intravenous thrombolysis with alteplase. Novel agents, including icatibant, are recommended in resistant patients with alteplase-induced OA who have failed to respond to first-line therapies including corticosteroids, antihistamines, and/or adrenaline. METHODS: We present a patient with alteplase-induced OA who showed substantial clinical improvement following the administration of icatibant. RESULTS: We describe a 71-year-old woman with known arterial hypertension under treatment with angiotensin-converting enzyme inhibitor, who presented with acute ischemic stroke in the territory of the right middle cerebral artery and received intravenous alteplase. During intravenous thrombolysis, the case was complicated with OA without any response to standard anaphylactic treatment including corticosteroids, dimetindene, and adrenaline. Thirty minutes after symptom onset, icatibant, a synthetic selective bradykinin B2-receptor antagonist, was administered subcutaneously. Substantial symptomatic resolution was observed only following the icatibant administration. CONCLUSIONS: This case highlights the effectiveness of icatibant in the acute management of alteplase-induced OA. In particular, icatibant administration, following first-line therapies including corticosteroids, antihistamines, and/or adrenaline, may avert tracheostomy and intubation in resistant and refractory cases with OA following intravenous thrombolysis for acute ischemic stroke.

Reperfusion therapies in patients with acute ischaemic stroke and atrial fibrillation: data on safety and effectiveness from a multi-centre cohort study.

BACKGROUND: Intravenous thrombolysis (IVT) and/or endovascular therapy (EVT) are currently considered best practices in acute stroke patients. Data regarding the efficacy and safety of reperfusion therapies in patients with atrial fibrillation (AF) are conflicting as regards haemorrhagic transformation, mortality, and functional outcome. This study sought to investigate for any differences, in terms of safety and effectiveness, between AF patients with acute ischaemic stroke (AIS) treated and untreated with reperfusion therapies. METHODS: Data from two multicenter cohort studies (RAF and RAF-NOACs) on consecutive patients with AF and AIS were analyzed to compare patients treated and not treated with reperfusion therapies (IVT and/or EVT). Multivariable logistic regression analysis was performed to identify independent predictors for outcome events: 90-day good functional outcome and mortality. A propensity score matching (PSM) analysis compared treated and untreated patients. RESULTS: Overall, 441 (25.4%) were included in the reperfusion-treated group and 1,295 (74.6%) in the untreated group. The multivariable model suggested that reperfusion therapies were significantly associated with good functional outcome. Rates of mortality and disability were higher in patients not treated, especially in the case of higher NIHSS scores. In the PSM comparison, 173/250 patients (69.2%) who had received reperfusion therapies had good functional outcome at 90 days, compared to 146/250 (58.4%) untreated patients (p = 0.009, OR: 1.60, 95% CI:1.11-2.31). CONCLUSIONS: Patients with AF and AIS treated with reperfusion therapies had a significantly higher rate of good functional outcome and lower rates of mortality compared to those patients with AF and AIS who had undergone conservative treatment.

Challenges in diagnosis and management of cerebral venous thrombosis as underlying cause of lobar intracerebral hemorrhage.

OBJECTIVES: Cerebral venous thrombosis is an uncommon, yet life-threatening condition, affecting mainly young and middle-aged individuals. Moreover, it represents an underrecognised etiology of lobar intracerebral hemorrhage (ICH). The clinical course of CVT is variable in the first days after diagnosis and medical complications including pulmonary embolism (PE) may result in early neurological deterioration and death if left untreated. MATERIALS AND METHODS: Case report. RESULTS: We describe a 46-year-old man with acute left hemiparesis and dysarthria in the context of lobar ICH due to underlying CVT of Trolard vein. Diagnosis was delayed because of misinterpretation of the initial neuroimaging study. Subsequently, the patient rapidly deteriorated and developed submassive PE and left iliofemoral venous thrombosis in the setting of previously undiagnosed hereditary thrombophilia (heterozygous prothrombin gene mutation G2021A). Emergent aspiration thrombectomy was performed resulting in the successful management of PE. A follow-up MRI study confirmed the thrombosed Trolard vein, thus establishing the CVT diagnosis. Anticoagulation treatment was immediately escalated to enoxaparine therapeutic dose resulting in clinical improvement of neurological deficits. CONCLUSIONS: Delayed diagnosis of cerebral venous thrombosis with underlying causes of lobar ICH may result in dire complications. Swift initiation of anticoagulants is paramount even in patients with lobar intracerebral hemorrhage as the initial manifestation of cerebral venous thrombosis.

Carotid-cavernous fistula: A potential treatable cause of bilateral abducens palsy and conjunctival hyperemia.

OBJECTIVE: Carotid cavernous fistulas (CCFs) represent uncommon and anomalous communications between the carotid artery and the cavernous sinus. MATERIALS AND METHODS: Case report RESULTS: We present the clinical details and successful management of a previously healthy 44-year-old patient who presented with one-month worsening headache, bilateral abducens palsy and conjunctival injection. Imaging modalities including magnetic resonance imaging (MRI) with contrast and digital subtraction angiography (DSA) facilitated the diagnosis of CCF. The patient underwent endovascular coiling of the CCF, leading to neurological recovery and symptom remission. CONCLUSION: This case highlights the importance of promptly CCF diagnosis in patients with multiple cranial nerve palsies and conjunctival hyperemia. Moreover, it emphasizes the efficacy of endovascular coiling in achieving symptom remission.

Safety of COVID-19 vaccines in multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Data are sparse regarding the safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (MS). OBJECTIVE: To estimate (1) the pooled proportion of MS patients experiencing relapse among vaccine recipients; (2) the rate of transient neurological worsening, adverse events, and serious adverse events; (3) the previous outcomes of interest for different SARS-CoV-2 vaccine types. METHODS: Systematic review and meta-analysis of pharmacovigilance registries and observational studies. RESULTS: Nineteen observational studies comprising 14,755 MS patients who received 23,088 doses of COVID-19 vaccines were included. Mean age was 43.3 years (95% confidence interval (CI): 40-46.6); relapsing-remitting, secondary-progressive, primary-progressive MS and clinically isolated syndrome were diagnosed in 82.6% (95% CI: 73.9-89.8), 12.6% (95% CI: 6.3-20.8), 6.7% (95% CI: 4.2-9.9), and 2.9% (95% CI: 1-5.9) of cases, respectively. The pooled proportion of MS patients experiencing relapse at a mean time interval of 20 days (95% CI: 12-28.2) from vaccination was 1.9% (95% CI: 1.3%-2.6%; I2 = 78%), with the relapse risk being independent of the type of administered SARS-CoV-2-vaccine (p for subgroup differences = 0.7 for messenger RNA (mRNA), inactivated virus, and adenovector-based vaccines). After vaccination, transient neurological worsening was observed in 4.8% (95% CI: 2.3%-8.1%) of patients. Adverse events and serious adverse events were reported in 52.8% (95% CI: 46.7%-58.8%) and 0.1% (95% CI: 0%-0.2%) of vaccinations, respectively. CONCLUSION: COVID-19 vaccination does not appear to increase the risk of relapse and serious adverse events in MS. Weighted against the risks of SARS-CoV-2-related complications and MS exacerbations, these safety data provide compelling pro-vaccination arguments for MS patients.

Bilateral dural arteriovenous fistula diagnosed with neurovascular ultrasonography.

BACKGROUND: Intracranial dural arteriovenous fistulas (dAVFs) are pathological anastomoses between meningeal arteries and dural venous sinuses or cortical veins. Diagnosis of dAVFs can be challenging due to their broad range of clinical manifestations and the lack of specificity in their symptoms. We present a rare case of a patient with bilateral dAVFs, who was referred to our department for carotid doppler ultrasonography/transcranial color Doppler. CASE REPORT: A 67-year-old man was referred by his treating physician for neurovascular ultrasonography due to vision impairment associated with papilledema of both eyes. On ultrasound examination both external carotid arteries showed a "pseudo-internalization" pattern with high end-diastolic velocities and reduced resistance indices. Subsequent magnetic resonance and digital subtraction angiography revealed dAVF of both transverse sinuses, with occipital and medial meningeal arteries as feeders. CONCLUSIONS: Neurovascular sonography may serve as a screening and follow-up tool when a DAVF in the transverse sinus/sigmoid sinus is suspected.

CADASIL in Greece: Mutational spectrum and clinical characteristics based on a systematic review and pooled analysis of published cases.

BACKGROUND: Differences have been noted in the clinical presentation and mutational spectrum of CADASIL among various geographical areas. The aim of the present study was to investigate the mode of clinical presentation and genetic mutations reported in Greece. METHODS: After a systematic literature search, we performed a pooled analysis of all published CADASIL cases from Greece. RESULTS: We identified 14 studies that reported data from 14 families comprising 54 patients. Migraine with aura was reported in 39%, ischemic cerebrovascular diseases in 68%, behavioral-psychiatric symptoms in 47% and cognitive decline in 60% of the patients. The mean (±SD) age of onset for migraine with aura, ischemic cerebrovascular diseases, behavioral-psychiatric symptoms and cognitive decline was 26.2 ± 8.7, 49.3 ± 14.6, 47.9 ± 9.4 and 42.9 ± 10.3, respectively; the mean age at disease onset and death was 34.6 ± 12.1 and 60.2 ± 11.2 years. With respect to reported mutations, mutations in exon 4 were the most frequently reported (61.5% of all families), with the R169C mutation being the most common (30.8% of all families and 50% of exon 4 mutations), followed by R182C mutation (15.4% of all families and 25% of exon 4 mutations). CONCLUSIONS: The clinical presentation of CADASIL in Greece is in accordance with the phenotype encountered in Caucasian populations, but differs from the Asian phenotype, which is characterized by a lower prevalence of migraine and psychiatric symptoms. The genotype of Greek CADASIL pedigrees is similar to that of British pedigrees, exhibiting a high prevalence of exon 4 mutations, but differs from Italian and Asian populations, where mutations in exon 11 are frequently encountered.

Demyelination with autoimmune features: a distinct clinical entity? Results from a longitudinal cohort.

OBJECTIVE: CNS demyelinating syndromes occurring in the context of SLE may represent a manifestation of neuropsychiatric lupus, or an overlap of SLE and multiple sclerosis (MS). We evaluated prospectively patients presenting with demyelinating syndrome for clinical and serological evidence of SLE and characterized the evolution of their clinical syndrome to a defined disease. METHODS: Patients with CNS demyelinating syndromes not fulfilling the criteria for MS were evaluated in a rheumatology unit for features of SLE and followed longitudinally (enrolment period 2016-20). Clinical, laboratory and neuroimaging data were recorded at every visit, following multidisciplinary evaluation. At end of follow-up, patients were assessed for their final neurological and rheumatological diagnosis, and classified accordingly. RESULTS: A total of 79 patients were included in the study [91.1% female, mean (s.d.) age at first demyelinating episode 38.4 (10.3) years, median (interquartile range) observation period 39 (57) months]. At last follow-up, 38 patients (48.1%) had evolved into MS. Of the remaining patients, 7 (17.1%) had SLE, while 34 (82.9%) had features of systemic autoimmunity without fulfilling classification criteria for SLE. The most common rheumatological features of these patients were inflammatory arthritis (73.5%), acute cutaneous lupus (47.1%) and positive ANA (72.1%). Importantly, these patients were less likely to have elevated IgG index (odds ratio 0.11, 95% CI 0.04, 0.32) and positive oligoclonal bands (odds ratio 0.21, 95% CI 0.08, 0.55). CONCLUSION: A significant number of patients with demyelination do not fulfill criteria for either MS or SLE at follow-up. These patients exhibit lupus-like autoimmune features and may represent a distinct entity, 'demyelination with autoimmune features'.

Delayed recurrent enhancing white matter lesions complicating coiling of intracranial aneurysm.

BACKGROUND AND PURPOSE: In recent years, the use of coiling has gained increased popularity for the treatment of intracranial aneurysms, and stroke physicians are confronted with rare pathologies associated with this relatively new and evolving treatment method, such as embolization of pieces of the polymeric filaments from the coils and a subsequent inflammatory response. In particular, white matter enhancing lesions are a rare complication after aneurysm endovascular therapy (EVT), suggesting a foreign body reaction to shedding of hydrophilic coating from the endovascular devices into the blood stream. The description of such a case aims to raise the clinicians' awareness of the symptomatic delayed and recurring inflammatory changes that may occur after endovascular aneurysmal treatment with the use of coiling devices. CASE DESCRIPTION: A 64-year-old woman underwent coiling of a ruptured right posterior communicating artery aneurysm. She was asymptomatic after EVT. One year later, she presented with headache, acoustic hallucinations, paresthesias and left arm weakness. Brain magnetic resonance imaging (MRI) revealed multiple enhancing white matter lesions in the right hemisphere. She was treated with pulse intravenous methylprednisolone, followed by oral prednisolone; all clinical symptoms resolved and imaging findings improved substantially. Two years after tapering the steroids, follow-up symptoms recurred and repeat brain MRI revealed new enhancing white matter lesions. DISCUSSION AND CONCLUSIONS: There is an increasing number of similar reports of enhancing white matter lesions after coiling of intracranial aneurysms, with the incidence estimated to be between 0.5% and 2.3% in different cohort studies. Close monitoring for the appearance of new neurologic symptoms that could suggest delayed brain reactivity should be recommended.

Ultrasound Assessment of Extracranial Carotids and Vertebral Arteries in Acute Cerebral Ischemia.

Assessing ischemic etiology and mechanism during the acute phase of an ischemic stroke is crucial in order to tailor and monitor appropriate treatment and determine prognosis. Cervical Duplex Ultrasound (CDU) has evolved since many years as an excellent screening tool for the evaluation of extracranial vasculature. CDU has the advantages of a low cost, easily applicable, bed side examination with high temporal and spatial resolution and without exposing the patients to any significant complications. It represents an easily repeatable test that can be performed in the emergency room as a first-line examination of cervical artery pathology. CDU provides well validated estimates of the type of the atherosclerotic plaque, the degree of stenosis, as well as structural and hemodynamic information directly about extracranial vessels (e.g., subclavian steal syndrome) and indirectly about intracranial circulation. CDU may also aid the diagnosis of non-atherosclerotic lesions of vessel walls including dissections, arteritis, carotid-jugular fistulas and fibromuscular dysplasias. The present narrative review outlines all potential applications of CDU in acute stroke management and also highlights its potential therapeutic implications.

Anticoagulation After Stroke in Patients With Atrial Fibrillation.

Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P<0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.

Blood biomarkers in ischemic stroke: potential role and challenges in clinical practice and research.

Fast and accurate diagnosis of stroke is crucial for the immediate application of the right therapy to patients. However, rapid diagnosis is still a challenge since an ischemic stroke cannot be identified based only on clinical assessment. CT or MRI imaging is required to rule out hemorrhagic stroke since thrombolytic therapy can lead to increased intracranial bleeding and further aggravation of hemorrhagic stroke. In addition, clinical situations that imitate the signs and symptoms of stroke may also impede the rapid diagnosis and treatment of stroke victims. It is therefore of value to discover non-invasive tests that aim to quickly distinguish stroke from stroke mimics and distinguish ischemic from hemorrhagic stroke. Identifying blood biomarkers of stroke is an active area of research since their potential use is not limited to diagnosis and differentiation, but can be applied to prognosis and patient monitoring - monitoring the effectiveness of applied therapy and/or diagnose possible complications. However, their use has been limited so far not only for reasons related to patients and the disease (heterogeneity of stroke etiology, the complexity of the ischemic cascade, the impact of the blood-brain barrier (BBB) on diffusion of blood biomarkers, and difficulties in obtaining consent from stroke patients) but also for reasons that related to laboratory measurement of these biomarkers (pre-analytical and analytical issues as well as interpretation of laboratory measurements). Until today, many biomarkers have been identified, however none so far have shown sufficient sensitivity and specificity in order to be used in the clinical setting. In this review, we will focus on ischemic stroke and we aim to highlight these problems and also investigate if these are due to stroke complexity or due to our limited knowledge of pre-analytical requirements for many of these molecules and the questionable quality of the assays used.

Plasma Glial Fibrillary Acidic Protein in the Differential Diagnosis of Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Plasma GFAP (glial fibrillary acidic protein) has recently emerged as a potential biomarker for the differentiation of acute intracerebral hemorrhage (ICH) from acute ischemic stroke (AIS). We prospectively assessed the diagnostic accuracy of GFAP in the differential diagnosis of ICH. METHODS: Consecutive patients presenting to the emergency department within 6 hours from symptom onset were evaluated. All patients underwent extensive diagnostic work-up and were classified according to discharge diagnosis in AIS, ICH, subarachnoid hemorrhage, and stroke mimics. GFAP was also measured in healthy volunteers (controls). Baseline stroke severity was evaluated using National Institutes of Health Stroke Scale. Receiver operating characteristic curve analysis was used to identify the optimal cutoff point for the differentiation between subgroups. Correlation analyses of GFAP plasma concentrations with baseline National Institutes of Health Stroke Scale and onset to sampling time were performed with the nonparametric Spearman rank test and fractional polynomial regression, respectively. RESULTS: Our study population consisted of 270 individuals (AIS: 121, ICH: 34, stroke mimics: 31, subarachnoid hemorrhage: 5, controls: 79). No differences on baseline stroke severity and onset to sampling time were detected between AIS and ICH. Higher median plasma GFAP values were documented in ICH compared with AIS, stroke mimics, and controls (P<0.001). Receiver operating characteristic analysis highlighted a cutoff value of 0.43 ng/mL as the optimal threshold for the differentiation between ICH and AIS (sensitivity: 91%, specificity: 97%). No association was detected between plasma GFAP concentrations and baseline stroke severity for both AIS (P=0.515) and ICH (P=0.387). In the fractional polynomial analysis, the association between GFAP concentration and onset to sampling time was best described by a J-shaped curve for AIS and an inverted U-shaped curve for ICH, with a peak at 2 hours. CONCLUSIONS: Plasma GFAP seems to be a sensitive and specific biomarker for the differentiation of ICH from both AIS and other acute neurological disorders, with the optimal diagnostic yield being present in the second hour from symptom onset.

Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study.

BACKGROUND AND PURPOSES: This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. METHODS: The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P=0.10) for major bleedings. RESULTS: The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P=0.009) for ischemic outcome events and 0.407 (0.275-0.540; P=0.14) for hemorrhagic outcome events. CONCLUSIONS: In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings.

Anti-osteoporotic treatments in the era of non-alcoholic fatty liver disease: friend or foe.

Over the last years non-alcoholic fatty liver disease (NAFLD) has grown into the most common chronic liver disease globally, affecting 17-38% of the general population and 50-75% of patients with obesity and/or type 2 diabetes mellitus (T2DM). NAFLD encompasses a spectrum of chronic liver diseases, ranging from simple steatosis (non-alcoholic fatty liver, NAFL) and non-alcoholic steatohepatitis (NASH; or metabolic dysfunction-associated steatohepatitis, MASH) to fibrosis and cirrhosis with liver failure or/and hepatocellular carcinoma. Due to its increasing prevalence and associated morbidity and mortality, the disease-related and broader socioeconomic burden of NAFLD is substantial. Of note, currently there is no globally approved pharmacotherapy for NAFLD. Similar to NAFLD, osteoporosis constitutes also a silent disease, until an osteoporotic fracture occurs, which poses a markedly significant disease and socioeconomic burden. Increasing emerging data have recently highlighted links between NAFLD and osteoporosis, linking the pathogenesis of NAFLD with the process of bone remodeling. However, clinical studies are still limited demonstrating this associative relationship, while more evidence is needed towards discovering potential causative links. Since these two chronic diseases frequently co-exist, there are data suggesting that anti-osteoporosis treatments may affect NAFLD progression by impacting on its pathogenetic mechanisms. In the present review, we present on overview of the current understanding of the liver-bone cross talk and summarize the experimental and clinical evidence correlating NAFLD and osteoporosis, focusing on the possible effects of anti-osteoporotic drugs on NAFLD.

Immunogenicity of a seasonal influenza and a pneumococcal polysaccharide vaccine in multiple sclerosis patients under disease modifying therapies: A single-center prospective study.

BACKGROUND: Immunogenicity of influenza and pneumococcal vaccines varies and requires further elucidation in patients with multiple sclerosis (MS) under treatment with disease-modifying therapies (DMTs). METHODS: Adult MS patients who consented with vaccination after standard-of-care consultation by their treating physicians were enrolled. All received a single dose of an inactivated quadrivalent influenza vaccine and of the 23-valent pneumococcal vaccine. A blood sample was collected before and after four weeks of vaccination for measurement of antibodies against Influenza A, B and S. pneumoniae. Patients were followed-up for adverse events and MS relapse for 12 months. RESULTS: One hundred and seventy-two patients (65.7 % female, mean age 42 ± 13 years old, mean MS duration 7.6 ± 7.2 years, 81.4 % under DMTs) were enrolled from November 2019 to March 2020. Antibody measurements were available for 151 patients. Seropositivity for anti-PPSV23 did not differ between baseline and at 4 weeks of follow-up (n = 56, 37.1 %). There was a significant increase of absolute antibody titers post-vaccination for both influenza A and B (p < 0.001). For Influenza A, seropositivity was evident for 57 (37.7 %) patients at 4 weeks compared to 19 (12.6 %) patients at baseline (pMcNemar < 0.001). For Influenza Β, 110 (72.8 %) seroconverted 4 weeks after vaccination compared to 12 (7.9 %) at baseline (pMcNemar < 0.001). Interferon and fumarate did not affect influenza seroconversion while rituximab was associated with lower titers. Mild local AEs (pain, edema) were observed in 23.8 %; no severe AE was reported. Thirty-four patients (19.8 %) had a relapse during the 12-month follow-up; none was attributed to the vaccination. CONCLUSIONS: Seroconversion in MS patients on treatment was more frequent following influenza compared to PPSV23 vaccination. Rituximab had an effect on the height of the immune response. Better immunization coverage as well as future evaluation of the breadth of immune response elicited by immunization is necessary for these patients.

Symptomatic Unilateral Carotid Artery Disease: An Uncommon but Reversible Cause of Corticobasal Syndrome.

INTRODUCTION: Symptomatic carotid artery disease (CAD) represents an uncommon but treatable cause of corticobasal syndrome. CASE REPORT: We present the clinical details and successful management of a previously healthy 77-year-old patient who presented with 1-year cognitive dysfunction, alien limb syndrome, limb kinetic apraxia, and ipsilateral cortical sensory deficit, fulfilling the criteria of the diagnosis of probable corticobasal syndrome. Imaging modalities, including magnetic resonance imaging and time-of-flight magnetic resonance angiography, revealed acute external borderzone infarcts of the right hemisphere due to symptomatic CAD causing near occlusion of the vessel. The patient underwent a right carotid endarterectomy, leading to a marked improvement in mobility and neuropsychological evaluation. CONCLUSION: This case highlights the importance of swift diagnosis of symptomatic CAD in patients with corticobasal syndrome. Moreover, it emphasizes the efficacy of carotid endarterectomy in achieving symptom improvement in such cases.