Intraluminal carotid thrombus leading to postpartum stroke: a case study.

BACKGROUND: Intraluminal non-occlusive thrombus (ILT) is a rare cause of ischemic stroke. Although in most cases ILT is associated with arterial wall disorders, it has also been documented in patients with thrombophilic conditions. CASE REPORT: We present a case of carotid ILT in a 38-year-old puerperal woman with pregnancy-induced hypercoagulability. Following in vitro fertilization pregnancy, she experienced acute left-sided weakness 9 days after delivery. CT angiography revealed an intraluminal filling defect in the right carotid bulb, suggestive of a thrombus, along with ipsilateral MCA sub-occlusion. Mechanical thrombectomy was performed, achieving complete vessel recanalization without any endovascular intervention on the carotid ILT. Comprehensive evaluation excluded any underlying carotid vessel wall disease (such as atherosclerosis, inflammatory diseases, arterial dissection, focal dysplasia), inherited or acquired thrombophilia, and the sole prothrombotic risk factor identified was the puerperium. Histological thrombus analysis showed fibrin/platelet-rich material with significant macrophage infiltration (consistent with an intermediate/organized thrombus, suggesting potential embolization from a pre-existing carotid ILT). Anti-thrombotic treatment (acetylsalicylic acid 100 mg and enoxaparin 6000 UI) resulted in complete thrombus resolution at follow-up. CONCLUSION: ILT should be considered a potential case of embolic stroke in pregnancy or puerperium. Vessel imaging is essential for diagnosis. Histological thrombus analysis can provide insights into the pathophysiological mechanisms of stroke.

Exploring thrombus composition in cerebral venous thrombosis: the first case report with initial insights and implications for treatment advancements.

BACKGROUND: Endovascular thrombectomy (EVT) is a treatment option in patients with a cerebral venous thrombosis (CVT) who deteriorate despite anticoagulant treatment. Assessment of thrombus composition in CVT may provide insights into the pathophysiology of the disease and suggest new therapeutic strategies. CASE REPORT: A 47-year-old woman (smoking habit and estradiol/progesterone-releasing intra-uterine device) diagnosed with massive CVT underwent EVT (complete recanalization via aspiration catheter and stentriever) due to acute-onset left-sided weakness and dysarthria despite 72 h of full-dose subcutaneous low-molecular heparin. Two main reddish clots (maximum diameter 15 mm) were retrieved. Microscopic assessment showed an erythrocyte-rich thrombus (83.9% of entire thrombus surface) with layers of platelets/fibrin (lines of Zahn: 13.9% fibrin and 38.5% platelet [CD61+]). The immunological profile was dominated by neutrophils (30% MPO+), with neutrophil extracellular traps (NETs) in 1.9% of thrombus surface. T- (CD3+), B-lymphocytes (CD20+), and monocytes/macrophages (CD68+) were rather rare (2.2%, 0.7%, and 2.0% respectively). We found no evidence (0.0%) of hemosiderin and endothelial cells (CD34+). Full clinical recovery occurred prior to discharge. CONCLUSION: This is the first case report of a CVT with histologic assessment of the thrombus retrieved via EVT. Evaluating thrombi in CVT can provide key insights into disease pathophysiology and guide treatment advancements.

Safety and efficacy of endovascular thrombectomy for primary and secondary MeVO.

BACKGROUND: Medium-vessel occlusions (MeVO) are emerging as a new target for endovascular treatment (EVT). Primary MeVO occur de novo, while secondary MeVO arise from large vessel occlusion (LVO) through clot migration or fragmentation - spontaneously, following intravenous thrombolysis or EVT. We aimed to evaluate efficacy and safety of EVT in primary and EVT-induced secondary MeVO. METHODS: Retrospective single-center study on consecutive EVT-treated acute ischemic stroke, from 2019-to-2021. We considered: (1) exclusive-LVO, patients with LVO and - in case of residual distal occlusion - no rescue endovascular procedure; (2) primary MeVO: initial A2, A3, M2 non-dominant, M3, P2, P3 occlusions; (3) EVT-induced secondary MeVO, presenting LVO with subsequent (treated) EVT-induced MeVO. We compared (univariable/multivariable logistic regression) EVT efficacy (eTICI≥2b, 3-month modified Rankin Scale [mRS] 0-2) and safety (EVT-complications [vessel dissection, perforation, persistent-SAH], symptomatic ICH) in all MeVO versus exclusive-LVO, primary MeVO versus exclusive-LVO, EVT-induced secondary MeVO versus exclusive-LVO and EVT-induced secondary MeVO versus primary MeVO. RESULTS: We included 335 patients: 221 (66.0 %) exclusive-LVO and 114 (34.0 %) MeVO (55 [48.2 %] primary, 59 [51.8 %] secondary). Compared to exclusive-LVO, primary MeVO had higher rates of EVT complications (aOR 3.77 [95%CI 1.58-9.00],p=0.003), lower rates of eTICI≥2b (aOR 0.32 [95%CI 0.12-0.88],p=0.027) and mRS 0-2 (aOR 0.28 [95%CI 0.13-0.63],p=0.002). EVT-induced secondary MeVO had no major differences in efficacy and safety outcomes compared to exclusive-LVO, but a better mRS 0-2 (aOR 8.00 [95%CI 2.12-30.17],p=0.002) compared to primary MeVO. CONCLUSIONS: Primary and EVT-induced secondary MeVO showed different safety/efficacy EVT-related profiles. Dedicated randomized data are needed to identify the best acute reperfusion strategy in the two categories.

Perfusion Imaging Mismatch Profiles in the Early Thrombectomy Window: A Single-Center Analysis.

BACKGROUND: Little is known on the role of mismatch profile in patients undergoing early endovascular treatment (EVT). We aimed to describe pretreatment perfusion parameters and mismatch profiles in anterior circulation large vessel occlusion acute ischemic stroke undergoing EVT in the early time window and assess their association with time from stroke onset and outcomes. METHODS: Retrospective single-center study, including early (<6 hours) EVT-treated large vessel occlusion acute ischemic stroke with baseline perfusion data, assessing perfusion parameters (ischemic core volume, mismatch volume and mismatch ratio) and mismatch profiles (favorable versus unfavorable, based on criteria adopted in EXTEND-IA [Extending the Time for Thrombolysis in Emergency Neurological Deficits - Intra-Arterial], SWIFT PRIME [Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment], DEFUSE 3 [Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3], and DAWN [Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo] trials). We evaluated their association with time from stroke onset (rs [for parameters] or χ2 for trend [for profiles]) and association with modified Rankin Scale score >2, symptomatic intracranial hemorrhage, and mortality (multivariate regression analyses [each parameter/profile entered into a separate logistic regression model, adjusted for baseline variables associated with each outcome in the univariate analysis at the P<0.1 level]). RESULTS: Among 357 patients, unfavorable mismatch profiles ranged from 21% to 60%, depending on the criterion, and were not correlated with time from stroke onset (P=0.490). All individual perfusion parameters and unfavorable mismatch profiles were associated with poor functional outcome: ischemic core volume adjusted odds ratio (aOR), 1.49 ([95% CI, 1.13-1.97] P=0.005); penumbral volume aOR, 0.30 ([95% CI, 0.10-0.84] P=0.022); mismatch ratio aOR, 0.67 ([95% CI, 0.50-0.90] P=0.007); EXTEND-IA aOR, 2.61 ([95% CI, 1.23-5.51] P=0.012); SWIFT PRIME aOR, 2.50 ([95% CI, 1.30-4.57] P=0.006); DEFUSE 3 aOR, 2.28 ([95% CI, 1.14-4.57] P=0.020); and DAWN aOR, 4.19 ([95% CI, 2.13-8.26] P<0.001). EXTEND-IA and DEFUSE 3 unfavorable profiles were also independently associated with symptomatic intracranial hemorrhage (aOR, 3.82 [95% CI, 1.42-10.3]; P=0.008 and aOR, 2.83 [95% CI, 1.09-7.36]; P=0.033) and death (aOR, 3.26 [95% CI, 1.33-8.02]; P=0.010 and aOR, 2.52 [95% CI, 1.10-5.82]; P=0.030). CONCLUSIONS: Pretreatment perfusion parameters and mismatch profiles in early EVT-treated patients were not correlated with time from stroke onset but were independently associated with functional outcome. Mismatch assessment in the early time window may improve EVT patient selection, independently of onset-to-treatment time.

Reperfusion Treatments in Disabling Versus Nondisabling Mild Stroke due to Anterior Circulation Vessel Occlusion.

BACKGROUND: The benefit of distinguishing between disabling versus nondisabling deficit in mild acute ischemic stroke due to endovascular thrombectomy-targetable vessel occlusion (EVT-tVO; including anterior circulation large and medium-vessel occlusion) is unknown. We compared safety and efficacy of acute reperfusion treatments in disabling versus nondisabling mild EVT-tVO. METHODS: From the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register, we included consecutive acute ischemic stroke patients (2015-2021) treated within 4.5 hours, with full NIHSS items availability and score ≤5, evidence of intracranial internal carotid artery, M1, A1-2, or M2-3 occlusion. After propensity score matching, we compared efficacy (3-month modified Rankin Scale score of 0-1, modified Rankin Scale score of 0-2, and early neurological improvement) and safety (nonhemorrhagic early neurological deterioration, any intracerebral or subarachnoid hemorrhage, symptomatic intracranial hemorrhage, and death at 3-month) outcomes in disabling versus nondisabling patients-adopting an available definition. RESULTS: We included 1459 patients. Propensity score matched analysis of disabling versus nondisabling EVT-tVO (n=336 per group) found no significant differences in efficacy (modified Rankin Scale score 0-1: 67.4% versus 71.5%, P=0.336; modified Rankin Scale score 0-2: 77.1% versus 77.6%, P=0.895; early neurological improvement: 38.3% versus 44.4%, P=0.132) and safety (nonhemorrhagic early neurological deterioration: 8.5% versus 8.0%, P=0.830; any intracerebral hemorrhage or subarachnoid hemorrhage: 12.5% versus 13.3%, P=0.792; symptomatic intracranial hemorrhage: 2.6% versus 3.4%, P=0.598; and 3-month death: 9.8% versus 9.2%, P=0.844) outcomes. CONCLUSIONS: We found similar safety and efficacy outcomes after acute reperfusion treatment in disabling versus nondisabling mild EVT-tVO; our findings suggest to adopt similar acute treatment approaches in the 2 groups. Randomized data are needed to clarify the best reperfusion treatment in mild EVT-tVO.

Acute idiosyncratic liver injury after Cladribine treatment for multiple sclerosis: first case report and review on associated hepatic disorders.

In recent years, several disease-modifying therapies have been developed for the treatment of multiple sclerosis (MS). Cladribine transiently depletes B and T lymphocytes, with subsequent gradual cell recovery. No cases are reported in literature describing Cladribine drug-induced liver injury (DILI). We describe the case of a 19-year-old woman who developed acute idiosyncratic liver injury 12 days after treatment with Cladribine. Post-marketing adverse event reporting is of paramount importance to allow an early recognition and treatment. Moreover, evaluation of the physiopathological mechanism underlying drug-induced hepatic toxicity can provide clinicians with valuable instruments for prevention and treatment.

Ischemic Stroke and Vaccine-Induced Immune Thrombotic Thrombocytopenia following COVID-19 Vaccine: A Case Report with Systematic Review of the Literature.

INTRODUCTION: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a prothrombotic syndrome observed after adenoviral vector-based vaccines for severe acute respiratory syndrome coronavirus 2. It is characterized by thrombocytopenia, systemic activation of coagulation, extensive venous thrombosis, and anti-platelet factor 4 antibodies. Arterial thrombosis is less common and mainly affects the aorta, peripheral arteries, heart, and brain. Several cases of ischemic stroke have been reported in VITT, often associated with large vessel occlusion (LVO). Here, we describe a case of ischemic stroke with LVO after Ad26.COV2.S vaccine, then we systematically reviewed the published cases of ischemic stroke and VITT following COVID-19 vaccination. METHODS: We describe a 58-year-old woman who developed a thrombotic thrombocytopenia syndrome with extensive splanchnic vein thrombosis and ischemic stroke due to right middle cerebral artery (MCA) occlusion, 13 days after receiving Ad26.COV2.S vaccination. Then, we performed a systematic review of the literature until December 3, 2021 using PubMed and EMBASE databases. The following keywords were used: ("COVID-19 vaccine") AND ("stroke"), ("COVID-19 vaccine") AND ("thrombotic thrombocytopenia"). We have selected all cases of ischemic stroke in VITT. RESULTS: Our study included 24 patients. The majority of the patients were females (79.2%) and younger than 60 years of age (median age 45.5 years). Almost all patients (96%) received the first dose of an adenoviral vector-based vaccine. Ischemic stroke was the presenting symptom in 18 patients (75%). Splanchnic venous thrombosis was found in 10 patients, and cerebral venous thrombosis in 5 patients (21%). Most patients (87.5%) had an anterior circulation stroke, mainly involving MCA. Seventeen patients (71%) had an intracranial LVO. We found a high prevalence of large intraluminal thrombi (7 patients) and free-floating thrombus (3 patients) in extracranial vessels, such as the carotid artery, in the absence of underlying atherosclerotic disease. Acute reperfusion therapy was performed in 7 of the 17 patients with LVO (41%). One patient with a normal platelet count underwent intravenous thrombolysis with alteplase, while 6 patients underwent mechanical thrombectomy. A malignant infarct occurred in 9 patients and decompressive hemicraniectomy was performed in 7 patients. Five patients died (21%). CONCLUSION: Our study points out that, in addition to cerebral venous thrombosis, adenoviral vector-based vaccines also appear to have a cerebral arterial thrombotic risk, and clinicians should be aware that ischemic stroke with LVO, although rare, could represent a clinical presentation of VITT.

Assessing mood and cognitive functioning in acute stroke: clinical usability of a Visual Analogue Mood Scale (VAMS).

BACKGROUND: Patients suffering from stroke in the acute/post-acute phases often present with depressive mood - which negatively impacts on patients' prognosis. However, psychometric evaluation of mood in acute stroke patients may be challenging due to cognitive deficits. Tools investigating emotional states via a vertical analogue line may overcome language/visuo-spatial disorders. This study thus aimed at (a) investigating the clinical usability of a Visual Analogue Mood Scale (VAMS) in acute stroke patients and (b) investigating the interplay between mood and cognition in this population. METHODS: Forty-one acute stroke patients were compared to 41 age-, education- and sex-matched healthy participants (HPs) on the VAMS and on cognitive measures (mental performance in acute stroke, MEPS). A control line bisection (LB) task was administered to control for potential visuo-spatial deficits in patients. RESULTS: Patients reported higher depression levels than HPs (lower VAMS scores); this between-group difference stayed significant when covarying for LB scores. MEPS scores discriminated patients from HPs; among cognitive measures, only the Clock drawing test (CDT) was positively associated with VAMS scores. Lesion side did not affect patients' mood state; however, disease duration was inversely related to VAMS scores. DISCUSSION: The VAMS proved to be a suitable tool for assessing mood in acute stroke patients, as being independent from post-stroke cognitive sequelae. The CDT might represent an adequate measure of depression-induced, post-stroke cognitive efficiency decrease. Mood disorders might occur and thus should be adequately addressed also in post-acute phases - likely due to longer hospitalization times and regression of anosognosic features.

Insomnia in primary care: a survey conducted on Italian patients older than 50 years-results from the "Sonno e Salute" study.

Insomnia affects one-third of the adult population and is associated with multiple medical conditions. We conducted an observational epidemiological survey to assess (1) the prevalence of insomnia in an Italian group of patients aged over 50 years, presenting directly to the general physician (GP); (2) the association of insomnia with sleepiness and comorbidities; and (3) the pharmacological treatment. The study was carried out by GPs. Each GP was asked to enroll the first patient over 50 years old spontaneously presenting for any medical problems for 5 consecutive days. The Italian version of the Sleep Condition Indicator (SCI) was administered; daytime sleepiness was evaluated by a visual analogic scale (VAS). For every patient, GPs collected information regarding comorbidities and pharmacological treatment for insomnia and evaluated the severity of insomnia using the Clinical Global Impression Severity (CGI-S) scale. A total of 748 patients (mean age 65.12 ± 9.45 years) were enrolled by 149 GPs. Prevalence of insomnia was 55.3%. SCI, VAS, and CGI-S scores were highly correlated between each other (p < 0.0001). At general linear model analysis, the comorbidities more associated with the presence of insomnia were anxiety-depressive disorder (p < 0.001), other psychiatric disorders (p = 0.017), cardiovascular disorders (p = 0.006), and dementia (p = 0.027). A statistically significant correlation was found between SCI score and the use of benzodiazepines (p < 0.001), z-drugs (p = 0.012), antidepressants (p < 0.001), and melatonin-prolonged release (p < 0.001). Insomnia affects half of Italian primary care patients over 50 years and is frequently associated with different medical conditions, sleepiness, and use of multiple-often off-label-drugs.

Sleep disorders and mental health in hospital workers during the COVID-19 pandemic: a cross-sectional multicenter study in Northern Italy.

INTRODUCTION: From the beginning of the COVID-19 pandemic, healthcare workers had to face unprecedented emergency needs associated with an extraordinary amount of psychological distress. In this cross-sectional multicenter study, we investigated sleep disturbances, and the level of anxiety and depression among the healthcare and non-healthcare staff of three hospitals in Milan (Italy) during the COVID-19 outbreak. Moreover, we explored potential predisposing factors for affective symptoms and poor sleep. METHODS: Between June and July 2020, we administered an online questionnaire to evaluate the presence of sleep disorders (Pittsburgh Sleep Quality Index), insomnia (Sleep Condition Indicator), anxiety (State Trait Anxiety Inventory), and depression (Beck Depression Inventory-II). We used univariate and multivariate analysis to evaluate the association between the personal conditions and sleep and affective disorders. RESULTS: The 964 participants reported high rates of sleep disorders (80.3%)-mainly insomnia (30.5%)-anxiety (69.7%), and depression (32.8%). The multivariate analysis showed a strong association of sleep disorders, especially insomnia, with female gender (p = 0.004), divorced marital status (p = 0.015), self-isolation (p = 0.037), and chronic diseases (p = 0.003). Anxiety was significantly associated with teleworking (p = 0.001), while depressive symptoms were associated with self-isolation (p = 0.028), modified work schedules (p = 0.03), and chronic diseases (p = 0.027). CONCLUSION: In hospital workers, the high prevalence of sleep and psychiatric symptoms during the COVID-19 outbreak appears to be determined mainly by modifications of personal or work habits. Teleworking was associated with increased anxiety. An accurate planning of hospital activities and a psychological support are needed to prevent and manage sleep and mental disorders.

Clinical characteristics of a large cohort of patients with narcolepsy candidate for pitolisant: a cross-sectional study from the Italian PASS Wakix® Cohort.

INTRODUCTION: Narcolepsy is a chronic and rare hypersomnia of central origin characterized by excessive daytime sleepiness and a complex array of symptoms as well as by several medical comorbidities. With growing pharmacological options, polytherapy may increase the possibility of a patient-centered management of narcolepsy symptoms. The aims of our study are to describe a large cohort of Italian patients with narcolepsy who were candidates for pitolisant treatment and to compare patients' subgroups based on current drug prescription (drug-naïve patients in whom pitolisant was the first-choice treatment, switching to pitolisant from other monotherapy treatments, and adding on in polytherapy). METHODS: We conducted a cross-sectional survey based on Italian data from the inclusion visits of the Post Authorization Safety Study of pitolisant, a 5-year observational, multicenter, international study. RESULTS: One hundred ninety-one patients were enrolled (76.4% with narcolepsy type 1 and 23.6% with narcolepsy type 2). Most patients (63.4%) presented at least one comorbidity, mainly cardiovascular and psychiatric. Pitolisant was prescribed as an add-on treatment in 120/191 patients (62.8%), as switch from other therapies in 42/191 (22.0%), and as a first-line treatment in 29/191 (15.2%). Drug-naive patients presented more severe sleepiness, lower functional status, and a higher incidence of depressive symptoms. CONCLUSION: Our study presents the picture of a large cohort of Italian patients with narcolepsy who were prescribed with pitolisant, suggesting that polytherapy is highly frequent to tailor a patient-centered approach.

Outcome of a Real-World Cohort of Patients Subjected to Endovascular Treatment for Acute Ischemic Stroke.

OBJECTIVES: Ischemic stroke is a leading cause of death and disability worldwide. For patients with large vessel occlusion stroke, endovascular treatment is now the most effective treatment. We aimed to assess the outcome of patients undergoing endovascular treatment for large vessel occlusion stroke in a real-world setting, comparing our results with data from randomized clinical trials, and recognizing the factors associated with prognosis. MATERIALS AND METHODS: We retrospectively collected data on endovascular procedures performed in one comprehensive stroke center in consecutive patients presenting with large vessel occlusion stroke from January 2017 to January 2020. Data on baseline clinical, imaging, and treatment-related characteristics were recorded. Selection of patients and treatment approach was not standardized but followed current guidelines for ischemic stroke. Functional outcome was evaluated 3 months after endovascular treatment. Clinical, imaging and treatment-related variables associated to outcome were evaluated with univariate and multivariable analyses. RESULTS: Four hundred twelve patients were included in our study. Three-month functional independence was achieved in 50.5% of patients (50.3% in the anterior stroke and 52.1% in the posterior stroke subgroup). Successful arterial reperfusion was observed in 84.3% of patients. Age (odds ratio [OR] 0.41, 95% confidence interval [CI] 0.20-0.87, p = 0.020]), severe stroke at onset (OR 0.40, 95%CI 0.19-0.83), procedure related complications (OR 0.45, 95%CI 0.20-0.99), and good collateral circulation (OR 2.69, 95%CI 1.17-6.16) were associated with 3-month functional independence in multivariable model. CONCLUSIONS: Our real-world outcome results are in line with data from large randomized clinical trials on endovascular treatment for large vessel occlusion stroke.

Neurological manifestations in patients hospitalized with COVID-19: A retrospective analysis from a large cohort in Northern Italy.

SARS-CoV2 infection is a systemic disease that may involve multiple organs, including the central nervous system (CNS). Aims of our study are to describe prevalence and clinical features of neurological manifestations, mortality and hospital discharge in subjects hospitalized with COVID-19. All individuals admitted for to our hospital COVID-19 were retrospectively included. Patients were classified according to the symptoms at hospital entry in (1) isolated respiratory, (2) combined respiratory and neurologic, (3) isolated neurologic and (4) stroke manifestations. Descriptive statistics and nonparametric tests to compare the groups were calculated. Kaplan Meier probability curves and multivariable Cox regression models for survival and hospital discharge were applied. The analysis included 901 patients: 42.6% showed a severe or critical disease with an overall mortality of 21.2%. At least one neurological symptom or disease was observed in 30.2% of subjects ranging from dysgeusia/anosmia (9.1%) to postinfective diseases (0.8%). Patients with respiratory symptoms experienced a more severe disease and a higher in-hospital mortality compared to those who showed only neurologic symptoms. Kaplan Meier estimates displayed a statistically significant different survival among groups (p = 0.003): subjects with stroke had the worst. After adjusting for risk factors such as age, sex and comorbidity, individuals with isolated neurologic manifestations exhibited a better survival (aHR 0.398, 95% CI [0.206, 0.769], p = 0.006). Neurologic manifestations in COVID-19 are common but heterogeneous and mortality in subjects with isolated neurologic manifestations seems lower than in those with respiratory symptoms.

Mechanical thrombectomy with or without thrombolysis: A meta-analysis of RCTs.

BACKGROUND: Mechanical thrombectomy (MT) is effective in treating ischemic strokes due to large vessel occlusion. However, the risk-benefit ratio of intravenous thrombolysis (IVT) prior to MT is still unclear. Aim of the study was to provide a pooled analysis of only randomized controlled trials (RCTs) comparing direct MT (dMT) vs bridging treatment (IVT+MT). METHODS: PubMed, EMBASE and Cochrane Central were searched only for RCTs comparing IVT+MT vs dMT in ischemic stroke patients. Primary endpoint was functional independence at 90 days (mRS<3), while secondary endpoints were represented by successful recanalization (TICI>2a), mortality at 90 days and symptomatic intracranial hemorrhage (sICH). Odds ratios for endpoints were pooled with meta-analysis and compared between reperfusion strategies. RESULTS: The pooled analysis comprised 5 studies (n. patients = 1657). The rates for the primary endpoint were 39% and 34.5% for dMT and IVT+MT, respectively (OR 1.06; 95%CI 0.80-1.40). For the secondary endpoints, we did not observe significant differences between groups, even if the rate of successful recanalization was higher in IVT+MT treated patients (OR: 0.58; 95%CI 0.26-1.30;pheterogeneity = 0.002), without a significant increase in sICH rates (4.3% vs 5.5%; OR: 0.96; 95%CI 0.43-2.13;pheterogeneity = 0.26). Finally, mortality rates were 19.8% and 15.9% for dMT and IVT+MT, respectively. CONCLUSIONS: In this meta-analysis including only RCTs, dMT and bridging treatment were substantially equivalent for good functional outcome. IVT+MT was associated to higher rates of successful recanalization, even if not significant. Therefore, further adequately powered RCTs comparing dMT vs IVT+MT are warranted.

Endovascular treatment versus intravenous thrombolysis alone in isolated M2 occlusion: a meta-analysis.

BACKGROUND: Optimal reperfusion strategies for M2 occlusion are still uncertain, with previous studies questioning benefit of mechanical thrombectomy (MT) over intravenous thrombolysis alone (IVT). Here we systematically reviewed and meta-analyzed data from studies comparing IVT alone vs MT with/without previous IVT, to define risk/benefit profile of each paradigm. METHODS: The study followed PRISMA guidelines. PubMed, EMBASE, and Cochrane Central were searched only for RCTs comparing MT with or without IVT vs IVT alone in adults with acute ischemic stroke and M2 occlusion. Primary endpoint was functional independence at 90 days (modified Rankin Scale<3); secondary endpoints were represented by symptomatic intracranial hemorrhage (sICH) and good recanalization (TICI>2a). Odds ratios for endpoints were pooled with meta-analysis and compared between reperfusion strategies. RESULTS: Seven studies (n=779) were included, all of high quality. Rate of good functional outcome was similar for MT and IVT (62.4% vs 66.3%; OR=0.73; 95%CI: 0.38-1.41; pheterogeneity=0.008) (Fig. 1).sICH was significantly more frequent in the MT group (8.5%) vs IVT group (3%) (OR 2.76, 95%CI 1.19-6.36, pheterogeneity=0.14). Good recanalization (TICI>2a) rate was higher in MT group vs IVT alone group (81.2% vs 51.4%; OR 3.99; 95%CI: 1.98-8.94; pheterogeneity=0.80). CONCLUSIONS: IVT alone provides similar clinical benefit compared to MT with/without IVT in cases of M2 occlusion. MT quadruplicates rates of good recanalization, but triplicates risk of sICH. Further trials are needed to define if MT confers any advantage over IVT for M2 occlusion.

SARS-CoV-2 infection after alemtuzumab in a multiple sclerosis patient: milder disease symptoms in comparison with coinfected relatives: a case report and review of the literature.

Literature data reporting SARS-CoV-2 infection in multiple sclerosis (MS) patients recently treated with immunodepleting agents as cladribine and alemtuzumab are very limited. The relationship between iatrogenic immunodeficiency and risk related to SARS-CoV-2 infection and its severe complications is still not clear. Cautiously, the start of immunosuppressant drugs as alemtuzumab and cladribine during the current COVID-19 pandemic is not recommended unless treatment benefits significantly outweigh potential risks. We report the case of a 30-year-old female MS patient infected by SARS-CoV-2 virus 4 months after alemtuzumab II cycle, while she was still leukopenic and lymphopenic. She had no complications and also presented milder COVID-related signs and symptoms as compared to her coinfected relatives (father, mother and her partner). Anti-S1 and S2 SARS-CoV-2 antibodies, tested 1 month and a half after the infection, resulted positive. We review all cases reported in literature of SARS-CoV-2 infection in MS patients treated with alemtuzumab. None of them had complications or severe disease.

Coverage of the requirements of first and second level stroke unit in Italy.

BACKGROUND AND AIM: In the scientific literature, there is unanimous consensus that hospitalization in stroke unit (SU) is the most important treatment for stroke patients. In this regard, the Act number 70/2015 by the Italian government identified specific skills that contribute to a classification of SU and outlined a "hub and spoke" stroke network. The aim of our study was to check the coverage of requirements of first and second level SU in the national territory and to shed light on any deficit or misdistribution of resources. MATERIAL AND METHODS: In 2019, a survey on the current situation related to stroke care in Italy was carried out by the Italian Society of Neurology (SIN), The Italian Stroke Organization (ISO), and the Association for the Fight against Stroke (A.L.I.Ce). RESULTS: First level SU was found to be 58 against a requirement, according to the Act 70/2015, of 240. Second level SU was found to be 52 compared with an expected requirement of 60. Neurointerventionists were 280 nationally, with a requirement of 240. A misdistribution of resources within individual regions was often seen. CONCLUSIONS: The survey demonstrated a severe shortage of beds dedicated to cerebrovascular diseases, mainly because of lack of first level SU, especially in central and southern Italy. It also suggests that the current hub and spoke system is not yet fully implemented across the country and that resources should be better distributed in order to ensure uniform and fair care for all stroke patients on the whole territory.

Cardiac autonomic dynamics during sleep are lost in patients with TIA and stroke.

Ischaemic stroke is accompanied by important alterations of cardiac autonomic control, which have an impact on stroke outcome. In sleep, cardiac autonomic control oscillates with a predominant sympathetic modulation during REM sleep. We aimed to assess cardiac autonomic control in different sleep stages in patients with ischaemic stroke. Forty-five patients enrolled in the prospective, multicentre SAS-CARE study but without significant sleep-disordered breathing (apnea-hypopnea index < 15/hr) and without atrial fibrillation were included in this analysis. The mean age was 56 years, 68% were male, 76% had a stroke (n = 34, mean National Institutes of Health Stroke Scale [NIHSS] score of 5, 11 involving the insula) and 24% (n = 11) had a transitory ischaemic attack. Cardiac autonomic control was evaluated using three different tools (spectral, symbolic and entropy analysis) according to sleep stages on short segments of 250 beats in all patients. Polysomnographic studies were performed within 7 days and 3 months after the ischaemic event. No significant differences in cardiac autonomic control between sleep stages were observed in the acute phase and after 3 months. Predominant vagal modulation and decreased sympathetic modulation were observed across all sleep stages in ischaemic stroke involving the insula. Patients with ischaemic stroke and transitory ischaemic attack present a loss of cardiac autonomic dynamics during sleep in the first 3 months after the ischaemic event. This change could represent an adaptive phenomenon, protecting the cardiovascular system from the instabilities of autonomic control, or a risk factor for stroke, which precedes the ischaemic event.

Bridging versus Direct Mechanical Thrombectomy in Acute Ischemic Stroke: A Subgroup Pooled Meta-Analysis for Time of Intervention, Eligibility, and Study Design.

BACKGROUND AND AIM: The risk/benefit profile of intravenous thrombolysis (IVT) prior to endovascular thrombectomy (EVT) in acute ischemic stroke is still unclear. We provide a systematic review and meta-analysis including studies comparing direct EVT (dEVT) vs. bridging treatment (IVT + EVT), defining the impact of treatment timing and eligibility to IVT on functional status and mortality. METHODS: Protocol was registered with PROSPERO (CRD42019135915) and followed PRISMA guidelines. PubMed, EMBASE, and Cochrane Central were searched for randomized controlled trials (RCTs), retrospective, and prospective studies comparing IVT + EVT vs. dEVT in adults (≥18) with acute ischemic stroke. Primary endpoint was functional independence at 90 days (modified Rankin Scale <3); secondary endpoints were (i) good recanalization (thrombolysis in cerebral infarction >2a), (ii) mortality, and (iii) symptomatic intracranial hemorrhage (sICH). Subgroup analysis was performed according to study type, eligibility to IVT, and onset-to-groin timing (OGT), stratifying studies for similar OGT. ORs for endpoints were pooled with meta-analysis and compared between reperfusion strategies. RESULTS: Overall, 35 studies were included (n = 9,117). No significant differences emerged comparing patients undergoing dEVT and bridging treatment for gender, hypertension, diabetes, National Institute of Health Stroke Scale score at admission. Regarding primary endpoint, IVT + EVT was superior to dEVT (OR 1.44, 95% CI 1.22-1.69, p < 0.001, pheterogeneity<0.001), with number needed to treat being 18 in favor of IVT + EVT. Results were confirmed in studies with similar OGT (OR 1.66; 95% CI 1.21-2.28), shorter OGT for IVT + EVT (OR 1.53, 95% CI 1.27-1.85), and independently from IVT eligibility (OR 1.53, 95% CI 1.29-1.82). Mortality at 90 days was higher in dEVT (OR 1.38; 95% CI 1.09-1.75), but no significant difference was noted for sICH. However, considering data from RCT only, reperfusion strategies had similar primary (OR 0.91, 95% CI 0.6-1.39) and secondary endpoints. Differences in age and clinical severity across groups were unrelated to the primary endpoint. CONCLUSIONS: Compared to dEVT, IVT + EVT associates with better functional outcome and lower mortality. Post hoc data from RCTs point to substantial equivalence of reperfusion strategies. Therefore, an adequately powered RCTs comparing dEVT versus IVT + EVT are warranted.

Headache in neurological emergency.

Headache represents the second neurological cause of emergency room admittance. The differentiation of the small number of patients with life-threatening headaches from the overwhelming majority with benign primary headaches is an important problem in the emergency department since the misdiagnosis of a secondary headache can have serious consequences, including permanent neurologic deficits and death. The presence of one or more high-risk features (red flags) in patient clinical history or neurological examination warrants an urgent diagnostic workup including blood tests, neuroradiological studies, and lumbar puncture.