Stress hyperglycemia is associated with futile recanalization in patients with anterior large vessel occlusion undergoing mechanical thrombectomy.

INTRODUCTION: Mechanical thrombectomy (MT) is the standard treatment for acute ischemic stroke (AIS) due to anterior large vessel occlusion (LVO). Despite successful recanalization, some patients remain disabled after 3 months. Mechanisms that can cause futile recanalization (FR) are still largely unknown. We investigated if stress hyperglycemia might be associated with FR. PATIENTS AND METHODS: This is a retrospective analysis of consecutive patients with successful recanalization treated in four participating centers between January 2021 and December 2022. According to the modified Rankin scale (mRS) status at 3 months, patients were divided into two groups: FR, if mRS score >2, and useful recanalization (UR), if mRS score ⩽2. Stress hyperglycemia was estimated by the glucose-to-glycated hemoglobin ratio (GAR) index. RESULTS: A total of 691 subjects were included. At 3 months, 403 patients (58.3%) were included in the FR group, while the remaining 288 patients (41.7%) were included in the UR group. At the multivariate analysis, variables independently associated with FR were the following: age (OR 1.04, 95% CI 1.02-1.06, p < 0.001), GAR index (OR 1.08, 95% CI 1.03-1.14, p = 0.003), NIHSS at admission (OR 1.16, 95% CI 1.11-1.22; p < 0.001), and procedure length (OR 1.01, 95% CI 1.00-1.02; p = 0.009). We observed that the model combining age, GAR index, NIHSS at admission, and procedure length had good predictive accuracy (AUC 0.78, 95% CI 0.74-0.81). CONCLUSIONS: Stress hyperglycemia predicts FR in patients with successful recanalization after MT. Further studies should explore if managing stress hyperglycemia may reduce futile recanalization. Additionally, we recommend paying close attention to AIS patients with a GAR index greater than 24.8 who exhibit a high risk of FR.

Predictors of atrial fibrillation detection in embolic stroke of undetermined source patients with implantable loop recorder.

Background: Covert atrial fibrillation (AF) is a predominant aetiology of embolic stroke of undetermined source (ESUS). Evidence suggested that AF is more frequently detected by implantable loop recorder (ILR) than by conventional monitoring. However, the predictive factors associated with occult AF detected using ILRs are not well established yet. In this study we aim to investigate the predictors of AF detection in patients with ESUS undergoing an ILR. Methods: This observational multi-centre study included consecutive ESUS patients who underwent ILR implantation. The infarcts were divided in deep, cortical infarcts or both. The infarction sites were categorized as anterior and middle cerebral artery, posterior cerebral artery with and without brainstem/cerebellum involvement. Multivariable logistic regression analysis was performed to investigate variables associated with AF detection. Results: Overall, 3,000 patients were initially identified. However, in total, 127 patients who consecutively underwent ILR implantation were included in our analysis. AF was detected in 33 (26%) out of 127 patients. The median follow-up was 411 days. There were no significant differences in clinical characteristics and comorbidities between patients with and without AF detected. AF was detected more often after posterior cerebral artery infarct with brainstem/cerebellum involvement (p < 0.001) whereas less often after infarction in the anterior and middle cerebral artery (p = 0.021). Multivariable regression analysis demonstrated that posterior cerebral artery infarct with brainstem/cerebellum involvement was an independent predictor of AF detection. Conclusion: Our study showed that posterior circulation infarcts with brainstem/cerebellum involvement are associated with AF detection in ESUS patients undergoing ILR. Larger prospective studies are needed to validate our findings.

Isolated insular stroke: topography is the answer with respect to outcome and cardiac involvement.

Background and purpose: Isolated insular strokes (IIS) are a rare occurrence due to the frequent concomitant involvement of adjacent territories, supplied by the M2 segment of the middle cerebral artery (MCA), and clinical aspects are sometimes contradictory. We aimed to describe clinical and radiological characteristics of a pure IIS case series, focusing on its functional outcome and cardiac involvement. Methods: We identified 15 isolated insular ischemic strokes from a pool of 563 ischemic strokes occurred between January 2020 and December 2021. Data collection consisted of demographic and baseline clinical characteristics, comorbidities, electrocardiograms, echocardiograms, stroke topography and etiology, reperfusive treatments, and outcome measures. Descriptive statistical analysis was carried out. Results: Newly detected cardiovascular alterations were the prevalent atypical presentation. Cardioembolism was the most frequent etiology. Most of patients had major neurological improvement at discharge and good outcome at 3-months follow-up. Discussion and conclusion: IIS are extremely rare, representing according to our study about 2.6% ischemic strokes cases per year, and patients have peculiar clinical manifestations, such as dysautonomia and awareness deficits. Our data suggest the possibility for these patients to completely recover after acute ischemic stroke notwithstanding the pivotal role of the insula in cerebral connections and the frequent association with MCA occlusion. Moreover, given the central role of the insula in regulating autonomic functions, newly detected cardiac arrhythmias must be taken into consideration, as well as a full diagnostic work-up for the research of cardioembolic sources. To our knowledge, this is the largest monocentric case series of IIS and it might be useful for future systematic reviews.

NK Cell Levels Correlate with Disease Activity in Patients with Multiple Sclerosis on Ocrelizumab/Rituximab Therapy.

BACKGROUND: Recently, research on the pathogenesis of multiple sclerosis (MS) has focused on the role of B lymphocytes and the possibility of using specific drugs, such as Ocrelizumab and Rituximab, directed toward these cells to reduce inflammation and to slow disease progression. OBJECTIVE: We aimed to evaluate the effect of Ocrelizumab/Rituximab on laboratory immune parameters and identify the predictors of treatment responses. METHODS: A retrospective single-center study was conducted among patients who received infusion therapy with an anti-CD20 drug to treat MS. RESULTS: A total of 64 patients met the inclusion criteria, with 277 total cycles of therapy studied. Compared with the baseline values, anti-CD20 infusions resulted in absolute-value and percentage decreases in B lymphocyte levels and increased the absolute and percentage levels of NK cells 3 and 5 months after therapy (p < 0.001). After multivariate logistic regression analysis, a reduced percentage level of NK cells 3 months after infusion could predict disease activity 6 months after Ocrelizumab/Rituximab administration (p = 0.041). CONCLUSIONS: Lower percentage levels of NK cells 3 months after anti-CD20 infusion correlate with the presence of disease activity 6 months after therapy, confirming a possible protective role of NK cells in MS.

Comparison of pharmacokinetic properties of alteplase and tenecteplase. The future of thrombolysis in acute ischemic stroke.

INTRODUCTION: The drug most frequently used for thrombolysis in cases of acute ischemic stroke (AIS) is alteplase. However, there is moderate-to-high-quality evidence that tenecteplase has similar or higher efficacy and safety. With improved pharmacokinetic properties over alteplase, tenecteplase could be a significant advantage in treating AIS. AREAS COVERED: After conducting an extensive search on Scopus and PubMed, this manuscript reviews and compares the pharmacokinetic properties of alteplase and tenecteplase. Additionally, it provides information on pharmacodynamics, clinical efficacy, safety, tolerability, and drug-drug interactions. EXPERT OPINION: The pharmacokinetic profile of alteplase and tenecteplase is derived from studies in patients with acute myocardial infarction. Thanks to its pharmacokinetic properties, tenecteplase is the drug closest to being the ideal fibrinolytic for AIS. Its longer half-life enables a single-bolus administration, which is particularly useful in emergencies. Tenecteplase has proven to have a good efficacy and safety profile in randomized clinical trials. Although we are awaiting the results of the ongoing phase 3 randomized clinical trials, we believe that tenecteplase has the potential to revolutionize the treatment of AIS through thrombolysis.

Clinical and functional determinants of appropriate rehabilitation referrals after stroke: a single-center retrospective cohort study.

BACKGROUND: Rehabilitation is currently the best available treatment for post-stroke disability. There is, however, great variability in the proportion of patients accessing rehabilitation across high-income countries suggesting that factors not explained by facilities availability or guidelines diversity may intervene in decision-making. OBJECTIVES: To evaluate which factors are associated with appropriate post-stroke rehabilitation referrals in a tertiary stroke unit setting. METHODS: Retrospective single-center cohort study including patients admitted to the Stroke Unit of the "Santa Maria della Misericordia" University Hospital, Udine (IT) from January 1st to December 31st, 2019. Information regarding stroke severity (National Institute of Health Stroke Scale), functional assessment (modified Rankin scale [mRS] and Barthel index [BI]), length of hospital stay, and rehabilitation pathway was collected. Outcome was defined as referral to the appropriate rehabilitation pathway. Appropriateness was assessed comparing patient clinical information at discharge against local criteria for intensive vs. extensive rehabilitation. A mixed-linear effect model was built to explore NIHSS, mRS, and BI variation over time. Multivariable logistic regression was used to estimate the adjusted-odds ratio (OR) and 95% confidence interval (CI 95%) of appropriate assignment to rehabilitation pathways. RESULTS: 288 patients were included in the study (age 73.1 years, males 57.9%) and in 75.7%, the rehabilitation pathway assignment was appropriate. NIHSS at discharge was lower compared to admission but no effect of rehabilitation assignment was evident, while mRS scores at discharge and at three months were 2.6 (CI 95% 2.2; 3.0) and 2.1 (CI 95% 1.8; 2.5) higher compared to admission (p < 0.0001). Rehabilitation assignment effect on mRS was time dependent, resulting in an additional - 0.6 (CI 95% - 1.0; - 0.2) lowering at discharge for those appropriately assigned (p = 0.003), with a trend for significance at three months (p = 0.08). BI score was higher at discharge (p < 0.0001), and appropriate assignment was associated with higher scores (p = 0.01). Multivariate analysis showed that the OR of appropriate rehabilitation pathway assignment were reduced by higher mRS (0.60 [CI 95% 0.48; 0.76], p < 0.0001) and increased by higher NIHSS (1.11 [CI 95% 1.04; 1.19], p = 0.001) scores at discharge. The latter finding might be explained by the rehabilitation assessment focus on post-stroke motor symptoms captured by NIHSS. CONCLUSIONS: Higher mRS and lower NIHSS levels at discharge were independent predictors for inappropriate rehabilitation assignment after stroke in our cohort. These findings may reflect a therapeutic bias toward patients with higher post-stroke disability in a rehabilitation framework heavily tilted on post-stroke motor symptoms.

Ketogenic diet may improve sleep quality and daytime somnolence in patients affected by multiple sclerosis. Results of an exploratory study.

OBJECTIVE/BACKGROUND: Patients with multiple sclerosis (MS) frequently report sleep complaints. The ketogenic diet (KD) is safe and tolerable in MS patients. Our aim was: 1) to investigate the effects of KD on sleep complaints in patients affected by relapsing-remitting MS and 2) to verify if sleep changes can positively impact on psychological status and quality of life (QoL) in these patients. PATIENTS/METHODS: From January 2020 to November 2022, we consecutively enrolled 21 non-disabled or minimally disabled MS patients. We collected information regarding: 1) anthropometric measures; 2) psychological status by the Depression Anxiety Stress Scale-21; 3) QoL by the Multiple Sclerosis Quality of Life-54 (MSQOL-54); 4) subjective sleep complaints, i.e. sleep quality, by the Pittsburgh Sleep Quality Index (PSQI), and excessive daytime sleepiness (EDS), by the Epworth Sleepiness Scale (ESS). RESULTS: After 6 months of KD therapy, anthropometric measures considerably changed, psychological status significantly improved, and almost all the MSQOL-54 subscales ameliorated. Regarding sleep, we observed that the global PSQI (T0: 7.7 ± 3.1 versus T1: 4.4 ± 3.1, p = 0.002) and the ESS (T0: 7.5 ± 3.9 versus T1: 4.9 ± 3.2, p = 0.001) scores significantly decreased after KD therapy. At T1, only the global PSQI score was an independent predictor of anxiety, stress, and mental health. CONCLUSIONS: For the first time, we demonstrated that KD may improve sleep complaints in MS patients. In addition, KD seems to have a positive impact on psychological status and QoL of MS patients, mainly through improving sleep quality. Further controlled studies with larger sample sizes are needed to confirm these preliminary results.

The use of alteplase, although safe, does not offer clear clinical advantages when mild stroke is non-disabling.

Introduction: It is unknown whether alteplase is effective and safe in patients with mild acute ischemic stroke (AIS). Determining whether symptoms are "disabling" or not is a crucial factor in the management of these patients. This study aimed to investigate the efficacy and safety of alteplase in patients with mild, non-disabling AIS. Methods: We included all consecutive patients admitted for AIS at our institution from January 2015 to May 2022 who presented a baseline NIHSS score of 0-5 and fit the criteria to receive intravenous thrombolysis. In order to select only subjects with non-disabling AIS, we excluded patients who scored more than 1 point in the following NIHSS single items: vision, language, neglect, and single limb. Patients who scored at least 1 point in the NIHSS consciousness item were excluded as well. This study is a retrospective analysis of a prospectively collected database. Results: After the application of the exclusion criteria, we included 319 patients, stratified into patients receiving and not receiving alteplase based on non-disabling symptoms. The two groups were comparable regarding demographic and clinical data. Rates of a 3-month favorable outcome, defined as a 3-month mRS score of 0-1, were similar, being 82.3% and 86.1% in the treated and untreated patients, respectively. Hemorrhagic complications and mortality occurred infrequently and were not affected by alteplase treatment. Discussion: This observational study suggests that the use of alteplase, although safe, is not associated with a better outcome in highly selected patients with non-disabling AIS.

Stress hyperglycemia as a modifiable predictor of futile recanalization in patients undergoing mechanical thrombectomy for acute ischemic stroke.

Introduction: Mechanical thrombectomy (MT) is the first line treatment in acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Approximately half of patients treated with MT does not have a favorable outcome 3 months after stroke. The aim of this study was to identify predictors of futile recanalization (FR) in patients with LVO treated with MT. Methods: A retrospective analysis of consecutive patients with acute ischemic stroke due to anterior circulation LVO who underwent MT. Patients with a TICI score of 2b or 3 were included. We distinguished two groups, FR and meaningful recanalization (MR), according to patients' disability three months after stroke (FR: mRS score > 2; MR: mRS score < 2). Results: We enrolled 238 patients (FR, n = 129, 54.2%; MR, n = 109, 45.8%). Age (OR 1.05, 95% CI 1.01-1.09, p = 0.012), female sex (OR 2.43, 95% CI 1.12-5.30, p = 0.025), stress hyperglycemia, as measured by the GAR index, (OR 1.17, 95% CI 1.06-1.29, p = 0.002), NIHSS at admission (OR 1.15, 95% CI 1.07-1.25, p = 0.001) and time from symptoms onset to MT (OR 1.01, 95% CI 1.00-1.01, p = 0.020) were independent predictors of FR. The AUC for the model combining age, female sex, GAR index, NIHSS at admission and time from symptoms onset to MT was 0.81 (95% CI 0.76-0.87; p < 0.001). The optimal GAR index cut-off score to predict FR was 17.9. Discussion: FR is common after MT. We recognized older age, female sex and baseline NIHSS as non-modifiable predictors of FR. On the other hand, time from symptoms onset to MT and stress hyperglycemia were modifiable pre- and post-MT factors, respectively. Any effort should be encouraged to reduce the impact of these modifiable predictors.

Post-Stroke Status Epilepticus: Time of Occurrence May Be the Difference?

(1) Background: Stroke is one of the most frequent causes of status epilepticus (SE) in adults. Patients with stroke and SE have poorer prognosis than those with stroke alone. We described characteristics and prognosis of early- and late-onset post-stroke SE (PSSE). (2) Methods: We retrospectively analyzed consecutive stroke patients who experienced a first SE between August 2012 and April 2021, comparing clinical characteristics, stroke, and SE features between early- versus late-onset SE in relation to patients' outcome. (3) Results: Forty stroke patients experienced PSSE. Fourteen developed an early-onset SE (35%) and twenty-six a late-onset SE (65%). Early-onset SE patients had a slightly higher NIHSS score at admission (6.9 vs. 6.0; p = 0.05). Early-onset SE was more severe than late-onset, according to STESS (Status Epilepticus Severity Score) (3.5 vs. 2.8; p = 0.05) and EMSE (Epidemiology-based Mortality score in Status Epilepticus) score (97.0 vs. 69.5; p = 0.04); furthermore, it had a significant impact on disability at 3-month and 1-year follow-up (p = 0.03 and p = 0.02). SE recurrence and seizures relapse were observed mainly in cases of late-onset SE. (4) Conclusions: Early-onset SE seems to be associated with higher disability in short- and long-term follow-up as possible expression of severe acute brain damage.

Hyperdense middle cerebral artery sign predicts favorable outcome in patients undergoing mechanical thrombectomy.

Non-contrast computer tomography detects the presence of hyperdense middle cerebral artery sign (HMCAS). Studies on the prognostic value of HMCAS among patients undergoing mechanical thrombectomy (MT) are conflicting. A retrospective analysis of consecutive patients with acute ischemic stroke due to middle cerebral artery occlusion, presenting with or without HMCAS, who underwent MT, was performed. We enrolled 191 patients (HMCAS +, n = 140; HMCAS -, n = 51). Prevalence of successful recanalization was significantly higher in patients with HMCAS than in those without HMCAS (92.1% versus 74.5%, p = 0.001). Patients with HMCAS had a better clinical outcome than those HMCAS - (54.3% versus 37.3%, p = 0.037, for three-month favorable outcome; 62.9% versus 39.3%, p = 0.004, for major neurological improvement at discharge; 8.6% versus 19.6%, p = 0.035, for in-hospital mortality; 14.3% versus 27.5%, p = 0.035, for intracranial hemorrhage; 2.9% versus 17.6%, p = 0.001, for symptomatic intracranial hemorrhage). Multivariate analyses confirmed that HMCAS represents an independent predictor of three-month favorable outcome (OR 2.48, 95% CI 1.10-5.58, p = 0.028), major neurological improvement at discharge (OR 2.40, 95% CI 1.09-5.20, p = 0.030), in-hospital mortality (OR 0.29, 95% CI 0.010-0.81, p = 0.018), presence of ICH (OR 0.49, 95% CI 0.25-0.97, p = 0.042) and presence of SICH (OR 0.16, 95% CI 0.04-0.63, p = 0.009). HMCAS presence predicts favorable outcome in patients undergoing MT. This result may indicate that hyperdense clots are more likely to respond to MT than isodense ones. This effect is mediated by reduction in hemorrhagic transformation.

The impact of COVID-19 on myocardial infarctions, strokes and out-of-hospital cardiopulmonary arrests: an observational retrospective study on time-sensitive disorders in the Friuli Venezia Giulia region (Italy).

The COVID-19 global pandemic has changed considerably the way time-sensitive disorders are treated. Home isolation, people's fear of contracting the virus and hospital reorganisation have led to a significant decrease in contacts between citizens and the healthcare system, with an expected decrease in calls to the Emergency Medical Services (EMS) of the Friuli-Venezia Giulia (FVG) region. However, mortality in clinical emergencies like acute ST-elevation myocardial infarction (STEMI), stroke and out-of-hospital cardiopulmonary arrest (OHCA) remained high. An observational retrospective cross-sectional study was carried out in FVG, taking into account the period between March 1, 2020, and May 31, 2020, the first wave of the COVID-19 pandemic, and comparing it with the same period in 2019. The flow of calls to the EMS was analysed and COVID-19 impact on time-sensitive disorders (STEMIs, ischemic strokes and OHCPAs) was measured in terms of hospitalisation, treatment and mortality. Despite a -8.01% decrease (p value ˂0.001) in emergency response, a 10.89% increase in calls to the EMS was observed. A lower number of advanced cardiopulmonary resuscitations (CPR) (75.8 vs 45.2%, p=0.000021 in April) and ROSC (39.1 vs 11.6%, p=0.0001 in April) was remarked, and survival rate dropped from 8.5 to 5%. There were less strokes (-27.5%, p value=0.002) despite a more severe onset of symptoms at hospitalisation with NHISS˃10 in 38.47% of cases. Acute myocardial infarctions decreased as well (-20%, p value=0.05), but statistical significances were not determined in the variables considered and in mortality. Despite a lower number of emergency responses, the number of calls to the EMS was considerably higher. The number of cardiac arrests treated with advanced CPR (ALS) was lower, but mortality was higher. The number of strokes decreased as well, but at the time of hospitalisation the clinical picture of the patient was more severe, thus affecting the outcome when the patient was discharged. Finally, STEMI patients decreased; however, no critical issues were observed in the variables taken into account, neither in terms of response times nor in terms of treatment times.

Contribution and Effectiveness of Laboratory Testing in the Diagnostic Assessment of Juvenile Ischemic Stroke and Transient Ischemic Attack.

Introduction Strokes in young people require an extensive diagnostic workup to detect their possible several etiopathogenetic mechanisms. There is no consensus indicating what and when it should be tested. The clinical benefit and cost-effectiveness ratio of laboratory tests is unclear as well. Methods In one series of 104 consecutive juvenile ischemic stroke patients, under 45 years old, admitted between January 1, 2012, and December 31, 2017, we considered a wide panel of laboratory biomarkers exploring both the patient's basal status and specific risk factors for thrombotic disorders. To combine conventional and unconventional risk factors, structural defects, and other stroke-related diseases, we defined four categories of etiologic probability. We then studied the contribution of laboratory testing in changing the rate of "definite or probable stroke etiology" and the "proportion of patients with at least one additional risk factor" for stroke. Results The mere clinical assessment clarified stroke etiopathogenesis in 31% of cases. Abnormal values of the panel of biomarkers we considered were found in 30.1% of young ischemic strokes, while 11.5% of patients had unclear or borderline values. The benefit of laboratory assessment consisted of a relevant 14% gain in patients with a "definite or probable stroke etiology." Conclusion Several areas of uncertainty are still pending and herein discussed, such as the low re-testing rate during follow-up and the neglect of some relevant biomarkers. However, our results support the importance of laboratory testing in this setting. An improvement of diagnostic protocols in juvenile ischemic stroke would even increase their effectiveness, and this is still an unsolved issue in the field of cerebrovascular diseases. The same age limit, conventionally considered for juvenile stroke, could be better defined according to the effectiveness of both laboratory and clinical assessment in identifying unconventional stroke risk factors.

Stress Hyperglycemia Does Not Affect Clinical Outcome of Diabetic Patients Receiving Intravenous Thrombolysis for Acute Ischemic Stroke.

Although stress hyperglycemia represents a main risk factor for poor outcome among patients with acute ischemic stroke (AIS) undergoing recanalization therapy, we have limited information regarding a possible influence of the premorbid diabetic status on this association. We recruited consecutive patients admitted to the Udine University Hospital with AIS who were treated with intravenous thrombolysis (IVT) from January 2015 to September 2020. On the basis of the premorbid diabetic status, our sample was composed of 130 patients with and 371 patients without diabetes. The glucose-to-glycated hemoglobin ratio (GAR) was used to measure stress hyperglycemia. Patients were stratified into 3 groups by tertiles of GAR (Q1-Q3). The higher GAR index was, the more severe stress hyperglycemia was considered. Among diabetic patients we did not observe any significant association between severe stress hyperglycemia and outcome measures (three-month poor outcome: Q1, 53.7%; Q2, 53.5%; Q3, 58.7%; p = 0.854; three-month mortality: Q1, 14.6%; Q2, 9.3%; Q3, 23.9%; p = 0.165; symptomatic intracranial hemorrhage: Q1, 7.3%; Q2, 14%; Q3, 19.6%; p = 0.256). Differently, non-diabetic subjects with more severe stress hyperglycemia showed a higher prevalence of three-month poor outcome (Q1, 32.2%; Q2, 27.7%; Q3, 60.3%; p = 0.001), three-month mortality (Q1, 9.1%; Q2, 8.4%; Q3, 18.3%; p = 0.026), and symptomatic intracranial hemorrhage (Q1, 0.8%; Q2, 0.8%; Q3, 9.9; p = 0.001). After controlling for several confounders, severe stress hyperglycemia remained a significant predictor of three-month poor outcome (OR 2.1, 95% CI 1.03-4.28, p = 0.041), three-month mortality (OR 2.39, 95% CI 1.09-5.26, p = 0.029) and symptomatic intracranial hemorrhage (OR 12.62, 95% CI 1.5-106, p = 0.02) among non-diabetics. In conclusion, premorbid diabetic status seems to influence outcome in AIS patients receiving IVT. Indeed, odds of functional dependency, mortality and hemorrhagic complications were significantly increased in patients with more severe stress hyperglycemia only when they were not affected by diabetes.

Posterior Reversible Encephalopathy Syndrome in Guillain-Barré Syndrome: Just a Problem of Immunoglobulins? Controversy From Two Atypical Case Reports.

Background: Posterior reversible encephalopathy syndrome (PRES), reversible cerebral vasoconstriction syndrome (RCVS), or the coexistence of these two entities shares similar risk factors and clinical features. For these conditions, a common origin has been supposed. Even if the majority of patients show a favorable course and a good prognosis, a small percentage of cases develop neurological complications. Up to date, only about 30 cases of PRES associated with Guillain-Barré syndrome (GBS) have been reported in the literature. Cases: Here, we present two cases of a particularly aggressive PRES/RCVS overlap syndrome, associated with acute motor axonal neuropathy (AMAN) and acute inflammatory demyelinating polyneuropathy (AIDP) variants of GBS, respectively, presenting with similar initial clinical aspects and developing both an atypical and unfavorable outcome. On MRI examination, the first patient showed typical aspects of PRES, while, in the second case, radiological features were atypical and characterized by diffusion restriction on the apparent diffusion coefficient (ADC) map. The first patient demonstrated rapid worsening of clinical conditions until death; the second one manifested and maintained neurological deficits with a permanent disability. Conclusions: We suggest that PRES may conceal RCVS aspects, especially in most severe cases or when associated with a dysimmune syndrome in which autoimmune system and endothelial dysfunction probably play a prominent role in the pathogenesis. Although the role of IVIg treatment in the pathogenesis of PRES has been proposed, we suggest that GBS itself should be considered an independent risk factor in developing PRES.

Opportunities and Obstacles Associated With Sequential Immune Reconstitution Therapy for Multiple Sclerosis: A Case Report.

Cladribine is an effective disease-modifying treatment for relapsing-remitting multiple sclerosis that acts as an immune reconstitution therapy and is administered in a pulsed manner. Despite its efficacy, severe disease reactivation early after treatment represents a serious clinical problem, and clear evidence to guide the management of such a situation is lacking. Here, we describe the case of a patient experiencing considerable disease activity during the 1st year after the initiation of cladribine treatment. The patient was switched to alemtuzumab and, therefore, received double immune reconstitution therapy. Data regarding this approach are lacking, and real-world observations may be of interest. Despite achieving good control of disease activity, we observed several serious infectious complications. Our results suggest that sequential immune reconstitution therapies may be effective; however, at the price of higher susceptibility to infections.

Stress Hyperglycemia in Patients With Acute Ischemic Stroke Due to Large Vessel Occlusion Undergoing Mechanical Thrombectomy.

Stress hyperglycemia may impair outcomes in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy (MT). The glucose-to-glycated hemoglobin ratio (GAR) was used to measure stress hyperglycemia. Data from our database of consecutive patients admitted to the Udine University Hospital with AIS who were treated with MT between January 2015 and December 2020 were retrospectively analyzed. We included 204 patients in the study and stratified them into four groups according to the quartiles of GAR (Q1-Q4). The higher the GAR index, the more severe the stress hyperglycemia was considered. Patients with more severe stress hyperglycemia showed a higher prevalence of 3-month poor outcome (Q1, 53.1%; Q2, 40.4%; Q3, 63.5%; Q4, 82.4%; p = 0.001), 3-month mortality (Q1, 14.3%; Q2, 11.5%; Q3, 15.4%; Q4, 31.4%; p = 0.001), and symptomatic intracranial hemorrhage (Q1, 2%; Q2, 7.7%; Q3, 7.7%; Q4, 25.4%; p = 0.001). After controlling for several confounders, severe stress hyperglycemia remained a significant predictor of 3-month poor outcome (OR 4.52, 95% CI 1.4-14.62, p = 0.012), 3-month mortality (OR 3.55, 95% CI 1.02-12.29, p = 0.046), and symptomatic intracranial hemorrhage (OR 6.89, 95% CI 1.87-25.36, p = 0.004). In summary, stress hyperglycemia, as measured by the GAR index, is associated with a detrimental effect in patients with AIS undergoing MT.

Cerebrovascular Risk in Restless Legs Syndrome: Intima-Media Thickness and Cerebral Vasomotor Reactivity: A Case-Control Study.

PURPOSE: Although some studies have suggested an association between cardiovascular disease and restless legs syndrome (RLS), the mechanisms underlying this relationship remain unclear. The intima-media thickness (IMT) and vasomotor reactivity are two simple, non-invasive tools to investigate preclinical atherosclerosis and microangiopathy, respectively. The aims of this study were to evaluate carotid IMT and to explore vasomotor reactivity in idiopathic RLS (iRLS) patients. PATIENTS AND METHODS: We enrolled 44 iRLS after exclusion of patients with secondary causes of RLS, history of vascular events, known uncontrolled vascular risk factors and other neurological disorders. Forty-four age and sex matched controls were therefore recruited. No significant differences in demographic data and vascular risk factors were found between the two groups. Carotid IMT was measured with a high-resolution B-mode ultrasound on the far-wall of common carotid artery, 10 mm and 30 mm to the carotid bulb. Vasomotor reactivity to hypo- and hypercapnia was assessed, by right middle cerebral artery transcranial Doppler, accordingly to the changes in peak systolic velocity, peak diastolic velocity and mean blood flow velocity. RESULTS: Mean IMT was significantly increased in patients with iRLS when measured immediately proximally to carotid bifurcation (0.73; sd=0.17), versus controls (0.65; sd=0.13); p=0.035. Patients showed higher cerebrovascular flow velocities (CBFVs) compared to controls. After multivariate analysis, age, hypertension and iRLS proved to be independent IMT predictors. CONCLUSION: Increased IMT and higher CBFVs in iRLS support the association of iRLS with vascular damage, possibly through enhanced atherogenesis and sympathetic hyperactivity. However, to clarify a causal relationship, further longitudinal assessment of these parameters is needed, trying to control all their physiological modifying factors.

Recanalisation theraphy for acute ischemic stroke in cancer patients.

To date, very few studies focused their attention on efficacy and safety of recanalisation therapy in acute ischemic stroke (AIS) patients with cancer, reporting conflicting results. We retrospectively analysed data from our database of consecutive patients admitted to the Udine University Hospital with AIS that were treated with recanalisation therapy, i.e. intravenous thrombolysis (IVT), mechanical thrombectomy (MT), and bridging therapy, from January 2015 to December 2019. We compared 3-month dependency, 3-month mortality, and symptomatic intracranial haemorrhage (SICH) occurrence of patients with active cancer (AC) and remote cancer (RC) with that of patients without cancer (WC) undergoing recanalisation therapy for AIS. Patients were followed up for 3 months. Among the 613 AIS patients included in the study, 79 patients (12.9%) had either AC (n = 46; 7.5%) or RC (n = 33; 5.4%). Although AC patients, when treated with IVT, had a significantly increased risk of 3-month mortality [odds ratio (OR) 6.97, 95% confidence interval (CI) 2.42-20.07, p = 0.001] than WC patients, stroke-related deaths did not differ between AC and WC patients (30% vs. 28.8%, p = 0.939). There were no significant differences between AC and WC patients, when treated with MT ± IVT, regarding 3-month dependency, 3-month mortality and SICH. Functional independence, mortality, and SICH were similar between RC and WC patients. In conclusion, recanalisation therapy might be used in AIS patients with nonmetastatic AC and with RC. Further studies are needed to explore the outcome of AIS patients with metastatic cancer undergoing recanalisation therapy.