Osteoarthritis in People with Multiple Sclerosis: A Systematic Review and Meta-Analysis.

Background: Arthritis, particularly osteoarthritis (OA), is a common synovial condition observed in individuals with multiple sclerosis (MS). Despite its high prevalence and significant impact on the quality of life of MS individuals, there is a gap in the current literature regarding the prevalence of OA in this population and its relation to MS pathology. This systematic review and meta-analysis aimed to estimate the prevalence of OA in the MS population and explore potential associations with demographic and MS-specific characteristics. Methods: Adhering to PRISMA guidelines, a systematic search of the MEDLINE PubMed, Scopus and Google Scholar databases was conducted. Results: Fifteen studies were included in the systematic review and meta-analysis. The aggregated prevalence of OA in the MS population was 27% (95% CI: 15-40%), with substantial heterogeneity (I2 = 99.9%). Sensitivity analysis, excluding one study, showed a prevalence of 21% (95% CI: 16-28%). The risk ratio of OA in MS versus controls was 1.07 (95% CI: 0.84-1.37), indicating no significant difference. Meta-regression revealed no associations between OA prevalence and age or disease duration in MS patients. Conclusions: This study reports a 21-27% prevalence of OA in people with MS. Understanding the implications of OA in pain and mobility domains, as well as the challenges in distinguishing OA symptoms from MS manifestations, underscores the need for further research to elucidate the pathophysiological mechanisms and interactions between these conditions. Additional studies are warranted to enhance clinical management and improve outcomes for individuals with MS and co-existing OA.

Heart failure and stroke: The underrepresentation of the heart failure with preserved ejection fraction subtype in randomized clinical trials of therapeutic anticoagulation.

Heart failure (HF) is an important comorbidity for patients with ischemic stroke, present in 11 %-18 % of patients, and may also independently increase the risk of first-ever and recurrent ischemic stroke. HF is categorized based on ejection fraction (EF) into HF with reduced (HFrEF), mildly-reduced (HFmrEG) and preserved ejection fraction (HFpEF), with the efficacy of HF therapies differing between the three subcategories. Despite this classification, the incidence, recurrence rates and outcomes of ischemic stroke do not appear to differ significantly between the three subtypes, even when considering the concurrent presence of atrial fibrillation. However, several randomized-controlled clinical trials of anticoagulation defined HF based on reduced EF, inevitably excluding a large proportion of patients with HFpEF. This exclusion is significant considering marked differences between heart failure phenotypes. Such discrepancies raise concerns about the broad applicability of the results of these studies, including those of primary or secondary stroke prevention in HF. Future trials should include both patients with HFrEF and HFpEF to evaluate the safety and efficacy of antiocoagulation therapies in primary and secondary stroke prevention across the spectrum of the EF.

From guidelines to clinical practice in care for ischaemic stroke patients: A systematic review and expert opinion.

BACKGROUND AND PURPOSE: Guidelines help physicians to provide optimal care for stroke patients, but implementation is challenging due to the quantity of recommendations. Therefore a practical overview related to applicability of recommendations can be of assistance. METHODS: A systematic review was performed on ischaemic stroke guidelines published in scientific journals, covering the whole acute care process for patients with ischaemic stroke. After data extraction, experts rated the recommendations on dimensions of applicability, that is, actionability, feasibility and validity, on a 9-point Likert scale. Agreement was defined as a score of ≥8 by ≥80% of the experts. RESULTS: Eighteen articles were identified and 48 recommendations were ultimately extracted. Papers were included only if they described the whole acute care process for patients with ischaemic stroke. Data extraction and analysis revealed variation in terms of both content and comprehensiveness of this description. Experts reached agreement on 34 of 48 (70.8%) recommendations in the dimension actionability, for 16 (33.3%) in feasibility and for 15 (31.3%) in validity. Agreement on all three dimensions was reached for seven (14.6%) recommendations: use of a stroke unit, exclusion of intracerebral haemorrhage as differential diagnosis, administration of intravenous thrombolysis, performance of electrocardiography/cardiac evaluation, non-invasive vascular examination, deep venous thrombosis prophylaxis and administration of statins if needed. DISCUSSION AND CONCLUSION: Substantial variation in agreement was revealed on the three dimensions of the applicability of recommendations. This overview can guide stroke physicians in improving the care process and removing barriers where implementation may be hampered by validity and feasibility.

Thrombolysis After Dabigatran Reversal for Acute Ischemic Stroke: A National Registry-Based Study and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Limited data exist on the safety of IV thrombolysis (IVT) for acute ischemic stroke (AIS) after dabigatran reversal with idarucizumab. We sought to evaluate the safety and efficacy of idarucizumab pretreatment in patients with AIS receiving IVT. METHODS: A national registry-based study evaluated the safety and efficacy of IVT in this specific subgroup. We also conducted a systematic review and meta-analysis of cohort studies and case series, aiming to document the pooled rates of (1) symptomatic intracranial hemorrhage (sICH), (2) any intracranial hemorrhage, (3) 3-month mortality, and (4) the proportion of excellent (modified Rankin Scale [mRS] scores 0-1) and (5) good (mRS scores 0-2) functional outcome at 3 months among patients with AIS, who received IVT after dabigatran reversal with idarucizumab. Moreover, we sought to compare these outcomes between IVT-treated patients after dabigatran reversal with idarucizumab and IVT-treated patients without dabigatran pretreatment. RESULTS: Thirteen cohorts including our nation-wide registry-based cohort and 1 case series comprising 553 patients with AIS (mean age: 75 years; male sex: 65%; median baseline NIH Stroke Scale score: 11 points) receiving idarucizumab before IVT were included in this meta-analysis. The pooled rate of sICH after IVT after idarucizumab administration was 4% (95% CI 1-9; I2 = 26%), while the pooled rates of any intracranial hemorrhage and 3-month mortality were 10% (95% CI 5-16; I2 = 24%) and 18% (95% CI 10-27; I2 = 0%), respectively. The pooled rates of excellent and good functional outcomes at 3 months were 56% (95% CI 27-83; I2 = 69%) and 70% (95% CI 57-81; I2 = 40%), respectively. The risk of sICH (risk ratio [RR] 1.86; 95% CI 0.91-3.80; I2 = 0%), any intracranial hemorrhage (RR 1.76; 95% CI 0.99-3.11; I2 = 8%), and 3-month mortality (RR 1.50; 95% CI 0.91-2.48; I2 = 0%) did not differ between patients with AIS receiving IVT with and without idarucizumab. Moreover, idarucizumab administration was associated with higher likelihood of achieving a 3-month good functional outcome (RR 1.35; 95% CI 1.11-1.65; I2 = 27%). DISCUSSION: IVT for AIS after dabigatran reversal with idarucizumab seems to be safe and effective in observational studies with limited number of patients. Randomized-controlled clinical trials are warranted to provide robust evidence on the safety and efficacy of IVT in this specific AIS subgroup.

Tibial nerve stimulation in the management of primary sexual dysfunction in patients with multiple sclerosis: a pilot randomized control trial.

INTRODUCTION: Sexual dysfunction (SD) is a common symptom that affects 40-90% of patients with multiple sclerosis (MS). Previous studies have highlighted the negative impact of sexual dysfunction in the mental health status and overall quality of life in patients with MS. METHODS: The aim of this study was to examine the effects of transcutaneous tibial nerve stimulation (TTNS) in the primary SD symptoms in patients with MS. A total of 40 participants were randomized (1:1 ratio) to either TTNS or Sham group and received three 20 min sessions over the course of two months. Pre and post intervention SD was evaluated using the Multiple Sclerosis Intimacy Questionnaire (MISQ-15). RESULTS: Statistically significant improvements in the aspects of primary sexual dysfunction were observed in the TTNS group pre-post intervention (specifically erectile function (for males)/vaginal lubrication (for females) (p < .001), orgasm quality and satisfaction for both male and female patients (p < .001), sexual desire (p < .05) and bladder related symptomatology (p < .005). In the sham group pre-post intervention, the only observed improvement was in the sexual desire aspect (p < .05). Post intervention the groups significantly differed erectile function/vaginal lubrication and orgasm quality and satisfaction (p < .05). CONCLUSIONS: Our findings underline the efficacy of TTNS in improving primary SD symptoms as well as bladder problems in both male and female patients with MS. TTNS demonstrated significant improvement in the following domains: erectile function, vaginal lubrication, orgasm quality, satisfaction, bladder-related symptoms, and sexual desire.

Collet-Sicard syndrome due to cervical artery dissection disclosed by high-resolution magnetic resonance imaging.

BACKGROUND AND PURPOSE: Cervical artery dissection (CAD) represents a leading cause of unilateral lower cranial nerve IX-XII palsy, known as Collet-Sicard syndrome (CSS). High-resolution magnetic resonance imaging (HR-MRI) is widely used in the evaluation of patients with CAD, providing information regarding vessel wall abnormalities and intraluminal thrombus. METHODS: We present a patient with palsy of multiple lower cranial nerves in the context of CSS, attributed to unilateral spontaneous internal carotid artery dissection. RESULTS: We describe a 68-year-old man with unremarkable previous history, who presented with subacute, gradually worsening dysphagia and hoarse voice. Clinical examination revealed right-sided palsy of cranial nerves IX-XII. Three-dimensional fat-saturated black-blood T1-weighted high-resolution vessel wall imaging disclosed spontaneous dissection with intramural hematoma along the distal right internal carotid artery. Neck MRI showed inward displacement of right aryepiglottic fold, right pyriform sinus dilatation, and right true vocal cord in middle position, indicative of right vagus nerve palsy, atrophy of right trapezius and sternocleidomastoid muscles, due to right spinal accessory nerve palsy, and unilateral tongue atrophy with fatty infiltration, characteristic for right hypoglossal nerve palsy. CONCLUSIONS: This case highlights the utility of high-resolution vessel wall imaging and especially fat-saturated T1-weighted black-blood SPACE (sampling perfection with application-optimized contrast using different flip-angle evolutions) sequences in the accurate diagnosis of CAD, revealing the characteristic mural hematoma and intimal flap. HR-MRI is also valuable in the recognition of indirect signs of lower cranial nerve compression.

European Stroke Organisation (ESO) and European Society for Minimally Invasive Neurological Therapy (ESMINT) guideline on acute management of basilar artery occlusion.

The aim of the present European Stroke Organisation (ESO) guideline is to provide evidence-based recommendations on the acute management of patients with basilar artery occlusion (BAO). These guidelines were prepared following the Standard Operational Procedure of the ESO and according to the GRADE methodology.Although BAO accounts for only 1-2% of all strokes, it has very poor natural outcome. We identified 10 relevant clinical situations and formulated the corresponding Population Intervention Comparator Outcomes (PICO) questions, based on which a systematic literature search and review was performed. The working group consisted of 10 voting members (five representing ESO and five representing the European Society of Minimally Invasive Neurological Therapy (ESMINT)) and three non-voting junior members. The certainty of evidence was generally very low. In many PICOs, available data were scarce or lacking, hence, we provided expert consensus statements.First, we compared intravenous thrombolysis (IVT) to no IVT, but specific BAO-related data do not exist. Yet, historically, IVT was standard of care for BAO patients who were also included (although in small numbers) in IVT trials. Non-randomized studies of IVT-only cohorts showed a high proportion of favorable outcomes. Expert Consensus suggests using IVT up to 24 hours unless otherwise contraindicated. We further suggest IVT plus endovascular treatment (EVT) over direct EVT. EVT on top of best medical treatment (BMT) was compared with BMT alone within 6 and 6-24 hours from last seen well. In both time windows, we observed a different effect of treatment depending on a) the region where the patients were treated (Europe vs Asia), b) on the proportion of IVT in the BMT arm, and c) on the initial stroke severity. In case of high proportion of IVT in the BMT group and in patients with a National Institutes of Health Stroke Scale (NIHSS) score below 10, EVT plus BMT was not found better than BMT alone. Based on very low certainty of evidence, we suggest EVT+BMT over BMT alone (this is based on results of patients with at least 10 NIHSS points and a low proportion of IVT in BMT). For patients with an NIHSS score below 10, we found no evidence to recommend EVT over BMT. In fact, BMT was non-significantly better and safer than EVT. Furthermore, we found a stronger treatment effect of EVT+BMT over BMT alone in proximal and middle locations of BAO compared with distal location. While recommendations for patients without extensive early ischemic changes in the posterior fossa can, in general, follow those of other PICOs, we formulated an Expert Consensus Statement suggesting against reperfusion therapy in those with extensive bilateral and/or brainstem ischemic changes. Another Expert Consensus suggests reperfusion therapy regardless of collateral scores. Based on limited evidence, we suggest direct aspiration over stent retriever as the first-line strategy of mechanical thrombectomy. As an Expert Consensus, we suggest rescue percutaneous transluminal angioplasty and/or stenting after a failed EVT procedure. Finally, based on very low certainty of evidence, we suggest add-on antithrombotic treatment during EVT or within 24 hours after EVT in patients with no concomitant IVT and in whom EVT was complicated (defined as failed or imminent re-occlusion, or need for additional stenting or angioplasty).

Diagnostic accuracy and confounders of vagus nerve ultrasound in amyotrophic lateral sclerosis-a single-center case series and pooled individual patient data meta-analysis.

BACKGROUND: Several single-center studies proposed utility of vagus nerve (VN) ultrasound for detecting disease severity, autonomic dysfunction, and bulbar phenotype in amyotrophic lateral sclerosis (ALS). However, the resulting body of literature shows opposing results, leaving considerable uncertainty on the clinical benefits of VN ultrasound in ALS. METHODS: Relevant studies were identified up to 04/2024 and individual patient data (IPD) obtained from the respective authors were pooled with a so far unpublished cohort (from Munich). An IPD meta-analysis of 109 patients with probable or definite ALS (El Escorial criteria) and available VN cross-sectional area (CSA) was performed, with age, sex, ALS Functional Rating Scale-revised (ALSFRS-R), disease duration, and bulbar phenotype as independent variables. RESULTS: Mean age was 65 years (± 12) and 47% of patients (± 12) had bulbar ALS. Mean ALSFRS-R was 38 (± 7), and mean duration was 18 months (± 18). VN atrophy was highly prevalent [left: 67% (± 5), mean CSA 1.6mm2 (± 0.6); right: 78% (± 21), mean CSA 1.8 mm2 (± 0.7)]. VN CSA correlated with disease duration (mean slope: left - 0.01; right - 0.01), but not with ALSFRS-R (mean slope: left 0.004; mean slope: right - 0.002). Test accuracy for phenotyping bulbar vs. non-bulbar ALS was poor (summary receiver operating characteristic area under the curve: left 0.496; right 0.572). CONCLUSION: VN atrophy in ALS is highly prevalent and correlates with disease duration, but not with ALSFRS-R. VN CSA is insufficient to differentiate bulbar from non-bulbar ALS phenotypes. Further studies are warranted to analyze the link between VN atrophy, autonomic impairment, and survival in ALS.

IL-6 Polymorphism as a Predisposing Genetic Factor for Gestational Diabetes or Preeclampsia Development in Pregnancy with Obesity in Relation to VEGF and VEGFF Receptor Gene Expression Modalities.

The increased prevalence of obesity worldwide has been implicated in the alarming rise of the incidence of gestational diabetes and preeclampsia, which are both considered threatening conditions for both mother and fetus. We studied gene polymorphisms of the proinflammatory cytokine Interleukin 6 (IL-6) and the gene expression levels of VEGF (vascular endothelial growth factor) and VEGF-R (endothelial growth factor receptor), all known to be involved in pregnancy complications, aiming to identify possible predisposing risk factors in pregnancies with obesity. The G allele of IL-6 was found to correspond with an increased risk for gestational diabetes and preeclampsia occurrence. Furthermore, in obese pregnant mothers with either gestational diabetes or pre-existing type 2 diabetes and those who developed preeclampsia, it was confirmed that gene expression levels of VEGF were reduced while they were increased for VEGF receptors. We conclude that the genetic profile of an obese pregnant woman shares a common background with that of a patient with pre-existing type 2 diabetes mellitus, and therefore predisposes them to complications in pregnancy.

Neuronal nicotinic acetylcholine receptor antibodies in autoimmune central nervous system disorders.

Background: Neuronal nicotinic acetylcholine receptors (nAChRs) are abundant in the central nervous system (CNS), playing critical roles in brain function. Antigenicity of nAChRs has been well demonstrated with antibodies to ganglionic AChR subtypes (i.e., subunit α3 of α3ß4-nAChR) and muscle AChR autoantibodies, thus making nAChRs candidate autoantigens in autoimmune CNS disorders. Antibodies to several membrane receptors, like NMDAR, have been identified in autoimmune encephalitis syndromes (AES), but many AES patients have yet to be unidentified for autoantibodies. This study aimed to develop of a cell-based assay (CBA) that selectively detects potentially pathogenic antibodies to subunits of the major nAChR subtypes (α4ß2- and α7-nAChRs) and its use for the identification of such antibodies in "orphan" AES cases. Methods: The study involved screening of sera derived from 1752 patients from Greece, Turkey and Italy, who requested testing for AES-associated antibodies, and from 1203 "control" patients with other neuropsychiatric diseases, from the same countries or from Germany. A sensitive live-CBA with α4ß2-or α7-nAChR-transfected cells was developed to detect antibodies against extracellular domains of nAChR major subunits. Flow cytometry (FACS) was performed to confirm the CBA findings and indirect immunohistochemistry (IHC) to investigate serum autoantibodies' binding to rat brain tissue. Results: Three patients were found to be positive for serum antibodies against nAChR α4 subunit by CBA and the presence of the specific antibodies was quantitatively confirmed by FACS. We detected specific binding of patient-derived serum anti-nAChR α4 subunit antibodies to rat cerebellum and hippocampus tissue. No serum antibodies bound to the α7-nAChR-transfected or control-transfected cells, and no control serum antibodies bound to the transfected cells. All patients positive for serum anti-nAChRs α4 subunit antibodies were negative for other AES-associated antibodies. All three of the anti-nAChR α4 subunit serum antibody-positive patients fall into the AES spectrum, with one having Rasmussen encephalitis, another autoimmune meningoencephalomyelitis and another being diagnosed with possible autoimmune encephalitis. Conclusion: This study lends credence to the hypothesis that the major nAChR subunits are autoimmune targets in some cases of AES and establishes a sensitive live-CBA for the identification of such patients.

CSF and plasma biomarkers in cerebral amyloid angiopathy: A single-center study and a systematic review/meta-analysis.

INTRODUCTION: There are limited data regarding cerebrospinal fluid (CSF) and plasma biomarkers among patients with Cerebral Amyloid Angiopathy (CAA). We sought to investigate the levels of four biomarkers [ß-amyloids (Aß42 and Aß40), total tau (tau) and phosphorylated tau (p-tau)] in CAA patients compared to healthy controls (HC) and patients with Alzheimer Disease (AD). PATIENTS AND METHODS: A systematic review and meta-analysis of published studies, including also a 5 year single-center cohort study, with available data on CSF and plasma biomarkers in symptomatic sporadic CAA versus HC and AD was conducted. Biomarkers' comparisons were investigated using random-effects models based on the ratio of mean (RoM) biomarker concentrations. RoM < 1 and RoM > 1 indicate lower and higher biomarker concentration in CAA compared to another population, respectively. RESULTS: We identified nine cohorts, comprising 327 CAA patients (mean age: 71 ± 5 years; women: 45%) versus 336 HC (mean age: 65 ± 5 years; women: 45%) and 384 AD patients (mean age: 68 ± 3 years; women: 53%) with available data on CSF biomarkers. CSF Aß42 levels [RoM: 0.47; 95% CI: 0.36-0.62; p < 0.0001], Aß40 levels [RoM: 0.70; 95% CI: 0.63-0.79; p < 0.0001] and the ratio Aß42/Aß40 [RoM: 0.62; 95% CI: 0.39-0.98; p = 0.0438] differentiated CAA from HC. CSF Aß40 levels [RoM: 0.73; 95% CI: 0.64-0.83; p = 0.0003] differentiated CAA from AD. CSF tau and p-tau levels differentiated CAA from HC [RoM: 1.71; 95% CI: 1.41-2.09; p = 0.0002 and RoM: 1.44; 95% CI: 1.20-1.73; p = 0.0014, respectively] and from AD [RoM: 0.65; 95% CI: 0.58-0.72; p < 0.0001 and RoM: 0.64; 95% CI: 0.57-0.71; p < 0.0001, respectively]. Plasma Aß42 [RoM: 1.14; 95% CI: 0.89-1.45; p = 0.2079] and Aß40 [RoM: 1.07; 95% CI: 0.91-1.25; p = 0.3306] levels were comparable between CAA and HC. CONCLUSIONS: CAA is characterized by a distinct CSF biomarker pattern compared to HC and AD. CSF Aß40 levels are lower in CAA compared to HC and AD, while tau and p-tau levels are higher in CAA compared to HC, but lower in comparison to AD patients.

Brainstem raphe hypoechogenicity is an independent predictor of post-stroke depression.

PURPOSE: Post-stroke depression (PSD) is a common complication after stroke and has a substantial effect on the quality of life of patients. Nevertheless, reliable individual prediction of PSD is not possible. As depressive symptoms have been associated with brainstem raphe (BR) hypoechogenicity on transcranial sonography (TCS), we aimed to explore the association of BR hypoechogenicity and the occurrence of PSD. MATERIALS AND METHODS: The Prognostic Markers of Post-Stroke Depression (PROMoSD) study is a prospective, observational, single-center, investigator-initiated study that included patients with acute ischemic stroke (AIS) to investigate the presence of BR hypoechogenicity by TCS early after symptom onset. The primary outcome was the presence of PSD assessed at the three-month follow-up investigation by a blinded psychiatrist and defined according to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V criteria). RESULTS: From 105 included AIS patients, 99 patients completed the study. AIS patients with a hypoechogenic BR developed a PSD at three months more frequently compared to patients with normal echogenicity (48.0% versus 4.1%, P <0.001). After adjustment for confounders (sex, mRS at follow-up, previous depressive episode), a hypoechogenic BR remained independently associated with a substantial increase in the appearance of PSD (adjusted OR: 6.371, 95%-CI: 1.181-34.362). CONCLUSION: A hypoechogenic BR is a strong and independent predictor of PSD at three months after AIS. TCS could be a routine tool to assess PSD risk in clinical practice, thereby streamlining diagnostic and therapeutic algorithms.

Combined Central and Peripheral Demyelination (CCPD) Associated with MOG Antibodies: Report of Four New Cases and Narrative Review of the Literature.

Background/Objectives: Myelin oligodendrocyte glycoprotein (MOG) is exclusively expressed in the central nervous system (CNS) and is found on the outer surface of oligodendrocytes. Antibodies to MOG are associated with CNS demyelination, whereas peripheral nervous system (PNS) demyelination is seldom reported to be related to MOG-IgG. Methods: The database of patients seen in our neurological academic center was searched for MOG-IgG seropositivity and concomitant demyelinating polyneuropathy. For the purpose of the review, in March 2024, we searched for case reports and case series in the following databases: PubMed, Scopus, Cochrane, and ScienceDirect. Inclusion criteria were MOG-IgG seropositivity and demyelinating polyneuropathy. Exclusion criteria were type of publication other than case reports and case series, unconfirmed diagnosis of demyelinating polyneuropathy, and other diseases causing demyelination in either the CNS or PNS. Critical appraisal of the selected case reports and case series was realized by JBI. Results: Four new cases were identified with MOG-IgG and confirmed demyelinating polyneuropathy. This review identified 22 cases that have been published since 2018. Clinical, imaging, neurophysiological, and immunological characteristics, as well as treatment options and outcomes are presented and compared to those of other cases with combined central and peripheral demyelination (CCPD). Conclusions: The pathogenetic mechanism is unclear; thus, different hypotheses are discussed. New case reporting and large cohort studies will help further the exploration of the underlying mechanism and guide more effective therapeutic interventions.

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.

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.

Hypoperfusion index ratio and pretreatment with intravenous thrombolysis are independent predictors of good functional outcome in acute ischemic stroke patients with large vessel occlusion treated with acute reperfusion therapies.

INTRODUCTION: We aimed to investigate the performance of several neuroimaging markers provided by perfusion imaging of Acute Ischemic Stroke (AIS) patients with large vessel occlusion (LVO) in order to predict clinical outcomes following reperfusion treatments. METHODS: We prospectively evaluated consecutive AIS patients with LVO who were treated with reperfusion therapies, during a six-year period. In order to compare patients with good (mRS scores 0-2) and poor (mRS scores 3-6) functional outcomes, data regarding clinical characteristics, the Alberta Stroke Programme Early Computed Tomography Score (ASPECTS) based on unenhanced computed tomography (CT), CT angiography collateral status and perfusion parameters including ischemic core, hypoperfusion volume, mismatch volume between core and penumbra, Tmax > 10 s volume, CBV index and the Hypoperfusion Index Ratio (HIR) were assessed. RESULTS: A total of 84 acute stroke patients with LVO who met all the inclusion criteria were enrolled. In multivariable logistic regression models increasing age (odds ratio [OR]: 0.93; 95%CI: 0.88-0.96, p = 0.001), lower admission National Institute of Health Stroke Scale (NIHSS)-score (OR: 0.88; 95%CI: 0.80-0.95, p = 0.004), pretreatment with intravenous thrombolysis (OR: 3.83; 95%CI: 1.29-12.49, p = 0.019) and HIR (OR:0.36; 95%CI: 0.10-0.95, p = 0.042) were independent predictors of good functional outcome at 3 months. The initial univariable associations between HIR and higher likelihood for symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma type 2 (PH2) were attenuated in multivariable analyses failing to reach statistical significance. DISCUSSION: Our pilot observational study of unselected AIS patients with LVO treated with reperfusion therapies demonstrated that pre-treatment low HIR in perfusion imaging and IVT were associated with better functional outcomes.

Timing of oral anticoagulants initiation for atrial fibrillation after acute ischemic stroke: A systematic review and meta-analysis.

INTRODUCTION: There is a longstanding clinical uncertainty regarding the optimal timing of initiating oral anticoagulants (OAC) for non-valvular atrial fibrillation following acute ischemic stroke. Current international recommendations are based on expert opinions, while significant diversity among clinicians is noted in everyday practice. METHODS: We conducted an updated systematic review and meta-analysis including all available randomized-controlled clinical trials (RCTs) and observational cohort studies that investigated early versus later OAC-initiation for atrial fibrillation after acute ischemic stroke. The primary outcome was defined as the composite of ischemic and hemorrhagic events and mortality at follow-up. Secondary outcomes included the components of the composite outcome (ischemic stroke recurrence, intracranial hemorrhage, major bleeding, and all-cause mortality). Pooled estimates were calculated with random-effects model. RESULTS: Nine studies (two RCTs and seven observational) were included comprising a total of 4946 patients with early OAC-initiation versus 4573 patients with later OAC-initiation following acute ischemic stroke. Early OAC-initiation was associated with reduced risk of the composite outcome (RR = 0.74; 95% CI:0.56-0.98; I2 = 46%) and ischemic stroke recurrence (RR = 0.64; 95% CI:0.43-0.95; I2 = 60%) compared to late OAC-initiation. Regarding safety outcomes, similar rates of intracranial hemorrhage (RR = 0.98; 95% CI:0.57-1.69; I2 = 21%), major bleeding (RR = 0.78; 95% CI:0.40-1.51; I2 = 0%), and mortality (RR = 0.94; 95% CI:0.61-1.45; I2 = 0%) were observed. There were no subgroup differences, when RCTs and observational studies were separately evaluated. CONCLUSIONS: Early OAC-initiation in acute ischemic stroke patients with non-valvular atrial fibrillation appears to have better efficacy and a similar safety profile compared to later OAC-initiation.