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Background: Cardiac involvement following an acute stroke (Stroke Heart Syndrome-SHS) is an established complication and it is linked to the involvement of sympathetic activation, inflammation, and neuro-endocrine response. Troponin "rise and fall pattern" > 30% is one marker of SHS. The aim of this study was to evaluate the role of reperfusion treatments in the prevention/pathogenesis of SHS with different stroke sizes and locations (OCSP classification)., Methods: We retrospectively analyzed data of 890 patients admitted to the Stroke Unit of Trieste (Italy) between 2018 and 2020. Out of them, 411 met the inclusion criteria (acute ischemic non-lacunar stroke). Clinical data were collected for each patient, imaging characteristics, and markers of cardiac injury [troponin I (TnI), NT-proBNP, "rise and fall pattern" > 30%]. We compared different stroke subtypes according to OCSP, while evaluating any differences in patients with and without SHS., Results: In treated total anterior circulation infarct (TACI) patients, the rate of SHS is lower than in non-treated TACI. Similar SHS rate was found in partial anterior (PACI) and posterior stroke (POCI), and between treated and non-treated patients. Focusing on TACI group, we compared SHS-TACI and non-SHS-TACI, we performed a univariate and multivariate analysis; treatment (OR 0.408 CI95% 0.185-0.900; p = 0.026) and diabetes (OR 2.618 CI95% 1.181-5.803; p = 0.018) were significantly associated to SHS. No clear insular effect was found in SHS development., Conclusions: In severe anterior stroke (TACI), reperfusion treatment may be effective in preventing SHS. Conversely, diabetes is an independent risk factor for SHS. PACI and POCI have similar troponin elevation rate., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives: A variety of neurologic disorders have been reported as presentations or complications of coronavirus disease 2019 (COVID-19) infection. The objective of this study was to determine their incidence dynamics and long-term functional outcome., Methods: The Neuro-COVID Italy study was a multicenter, observational, cohort study with ambispective recruitment and prospective follow-up. Consecutive hospitalized patients presenting new neurologic disorders associated with COVID-19 infection (neuro-COVID), independently from respiratory severity, were systematically screened and actively recruited by neurology specialists in 38 centers in Italy and the Republic of San Marino. The primary outcomes were incidence of neuro-COVID cases during the first 70 weeks of the pandemic (March 2020-June 2021) and long-term functional outcome at 6 months, categorized as full recovery, mild symptoms, disabling symptoms, or death., Results: Among 52,759 hospitalized patients with COVID-19, 1,865 patients presenting 2,881 new neurologic disorders associated with COVID-19 infection (neuro-COVID) were recruited. The incidence of neuro-COVID cases significantly declined over time, comparing the first 3 pandemic waves (8.4%, 95% CI 7.9-8.9; 5.0%, 95% CI 4.7-5.3; 3.3%, 95% CI 3.0-3.6, respectively; p = 0.027). The most frequent neurologic disorders were acute encephalopathy (25.2%), hyposmia-hypogeusia (20.2%), acute ischemic stroke (18.4%), and cognitive impairment (13.7%). The onset of neurologic disorders was more common in the prodromic phase (44.3%) or during the acute respiratory illness (40.9%), except for cognitive impairment whose onset prevailed during recovery (48.4%). A good functional outcome was achieved by most patients with neuro-COVID (64.6%) during follow-up (median 6.7 months), and the proportion of good outcome increased throughout the study period ( r = 0.29, 95% CI 0.05-0.50; p = 0.019). Mild residual symptoms were frequently reported (28.1%) while disabling symptoms were common only in stroke survivors (47.6%)., Discussion: Incidence of COVID-associated neurologic disorders decreased during the prevaccination phase of the pandemic. Long-term functional outcome was favorable in most neuro-COVID disorders, although mild symptoms commonly lasted more than 6 months after infection., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

By blocking the release of neurotransmitters, botulinum toxin A (BoNT-A) is an effective treatment for muscle over-activity and pain in stroke patients. BoNT-A has also been reported to increase passive range of motion (p-ROM), the decrease of which is mainly due to muscle shortening (i.e., muscle contracture). Although the mechanism of action of BoNT-A on p-ROM is far from understood, pain relief may be hypothesized to play a role. To test this hypothesis, a retrospective investigation of p-ROM and pain was conducted in post-stroke patients treated with BoNT-A for upper limb hypertonia. Among 70 stroke patients enrolled in the study, muscle tone (Modified Ashworth Scale), pathological postures, p-ROM, and pain during p-ROM assessment (Numeric Rating Scale, NRS) were investigated in elbow flexors (48 patients) and in finger flexors (64 patients), just before and 3-6 weeks after BoNT-A treatment. Before BoNT-A treatment, pathological postures of elbow flexion were found in all patients but one. A decreased elbow p-ROM was found in 18 patients (38%). Patients with decreased p-ROM had higher pain-NRS scores (5.08 ± 1.96, with a pain score ≥8 in 11% of cases) than patients with normal p-ROM (0.57 ± 1.36) ( p < 0.001). Similarly, pathological postures of finger flexion were found in all patients but two. A decreased finger p-ROM was found in 14 patients (22%). Pain was more intense in the 14 patients with decreased p-ROM (8.43 ± 1.74, with a pain score ≥ 8 in 86% of cases) than in the 50 patients with normal p-ROM (0.98 ± 1.89) ( p < 0.001). After BoNT-A treatment, muscle tone, pathological postures, and pain decreased in both elbow and finger flexors. In contrast, p-ROM increased only in finger flexors. The study discusses that pain plays a pivotal role in the increase in p-ROM observed after BoNT-A treatment.

Objective: To develop and validate a quick observational clinical tool, the Functional ASsessment Test for Upper Limb (FAST-UL), for the evaluation of upper limb impairment in goal-directed functional-oriented motor tasks after stroke., Design: Observational, cross-sectional, psychometric study., Setting: Inpatient and outpatient rehabilitation clinic., Participants: A total of 188 post-stroke survivors (mean age 65.2±17.7 years, 61% men, 48% with ischemic stroke and 66% in the sub-acute phase; N=188)., Interventions: Not applicable., Main Outcome Measures: Principal component analysis and Rasch analysis through a Partial Credit Model were used to assess the structure and psychometric properties of the 5 items of the FAST-UL (Hand to Mouth [HtM], Reach to Target, Prono-Supination, Grasp and Release, and Pinch and Release [PaR])., Results: The Cronbach's α equal to 0.96 was indicative of an acceptable internal consistency; the reliability, as measured through the Person Separation Reliability equal to 0.87, was good. The FAST-UL tool was unidimensional. All the FAST-UL items were found to fit well the Rasch measurement model. The easiest to perform FAST-UL item was the HtM movement while the most difficult was the PaR movement., Conclusions: The FAST-UL is a quick, easy-to-administer observational assessment tool of upper limb motor impairment in post-stroke survivors with good item-level psychometric properties., (Copyright © 2022 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Symptomatic intracerebral hemorrhage (sICH) and major bleeding can be fatal complications of intravenous thrombolysis (IVT) for acute ischemic stroke. We investigated the impact of early fibrinogen depletion after IVT on major bleeding events., Methods: This multicenter observational prospective cohort study enrolled 1678 consecutive patients receiving IVT for acute ischemic stroke at 6 Italian centers, undergoing fibrinogen concentration assessment at baseline, 2 hours and 6 hours after IVT. Fibrinogen depletion was defined as a reduction below 200 mg/dL after 2 hours from IVT, or as a reduction below 50% of baseline fibrinogen levels after 2 hours from IVT. Main outcomes were (1) sICH (National Institute of Neurological Disorders and Stroke criteria) and (2) major bleeding defined as fatal bleeding, decrease in the hemoglobin level>2 g/dL/>1 unit transfusion, or bleeding at critical site. Additional outcomes were (1) any ICH, (2) any bleeding, (3) fatal ICH, and (4) sICH according to ECASSII definition. Good functional recovery was defined as modified Rankin Scale score 0 to 2 at 3 months., Results: Overall, 1678 patients were included (mean age 72 years, 46% female). sICH (n=116) and major bleeding (n=297) were associated with lower rate of good functional recovery ( P <0.001). Despite similar fibrinogen levels at admission, fibrinogen depletion after 2 hours from IVT was more common in people with sICH, major bleeding and all additional bleeding outcomes. In the backward stepwise multivariable logistic regression model, fibrinogen depletion remained a significant predictor of sICH (OR, 1.55 [95% CI, 1.04-2.32]) and major bleeding (OR, 1.36 [95% CI, 1.03-1.8]). Thirty-one percent of sICH could be attributable to fibrinogen depletion. The association between fibrinogen depletion and worse clinical outcome at 3 months after stroke ( P =0.012) was attributable to the higher risk of major bleeding/sICH., Conclusions: Fibrinogen depletion significantly increases the risk of sICH and major bleeding after IVT for acute ischemic stroke. Fibrinogen depletion represents an independent risk factor for bleeding, and routine assessment could be considered to stratify the risk of ICH. Trials on early fibrinogen repletion are needed to investigate mitigation of bleeding risk.

Background: Enteral nutrition is often prescribed in acute stroke to meet energy and fluid needs in patients with dysphagia. Tubes clogging represent a common complication of enteral formula delivery, requiring substitution and influencing nutrition administration. Frequent water flushes are recommended as one of the most effective procedures to prevent tube occlusion, but it might be time demanding and not consistently performed by the healthcare staff. This study aimed to assess the efficacy of an automatic flush pump, compared to a manual flush system, to prevent tubes' occlusions in acute-stroke patients, as this might affect nutrition and hydration., Methods: Gastrointestinal symptoms, nutrition and hydration biomarkers were also monitored to determine the different devices' safety. Sixty-two patients were included in the study and allocated to the "manual" or "automatic" flushes device., Results: The mean duration of data collection was 7 ± 2 days. Tube occlusions occurred in 22.6% of the patients in the "manual" group, whereas only one tube clogging was reported in the "automatic" group ( p = 0.023). No significant differences between groups were reported for constipation and diarrhea frequency nor nutrition and hydration status. When the nurses were asked to simulate manual flush administration at the same frequency of the automatic device, they were able to meet the recommendations only 10% of the time., Conclusion: This preliminary study suggests the efficacy of automatic flush systems to prevent enteral tube clogging, without affecting health status compared to standard manual flush systems.

Objective Among the clinical manifestations of stroke mimics, isolated aphasia is one of the most challenging due to its aetiopathogenic diagnosis. This short communication describes a specific perfusion and brain oscillatory pattern in a challenging case of prolonged isolated aphasia caused by status epilepticus, jointly investigated by computed tomography (CT) perfusion, single-photon emission computerized tomography (SPECT)/CT and EEG qualitative and quantitative analysis. Methods We discuss the different patterns of perfusion neuroimaging and EEG between SE and ischaemic stroke or postictal (Todd's)-related isolated aphasia, and propose these differences as a basis to support the differential diagnosis. Results The pattern associated with SE was characterized by focal hyperperfusion on CT perfusion maps (the left mean transit time was shorter with >10% asymmetry, and left cerebral blood volume and cerebral blood flow increased or slightly altered, relative to the contralateral side) and SPECT (focal left temporal hyperperfusion), without any early ischaemic signs on non-enhanced CT, while the EEG showed a predominant left hemispheric slow delta power. The aforementioned perfusion pattern contrasts with postictal epileptic Todd's phenomenon, which is characterized by hypoperfusion on CT perfusion (the mean transit time is prolonged and cerebral blood volume and cerebral blood flow are reduced, compared to the contralateral hemisphere) and SPECT (focal hypoperfusion), not restricted to the specific vascular territories. Significance CT perfusion patterns may add valuable information to support the differential diagnosis of status epilepticus, rather than acute ischaemic stroke or postictal Todd's phenomenon, in cases with challenging symptoms of prolonged isolated aphasia.

Outcome prediction in wake-up ischemic stroke (WUS) is important for guiding treatment strategies, in order to improve recovery and minimize disability. We aimed at producing an interpretable model to predict a good outcome (NIHSS 7-day<5) in thrombolysis treated WUS patients by using Classification and Regression Tree (CART) method. The study encompassed 104 WUS patients and we used a dataset consisting of demographic, clinical and neuroimaging features. The model was produced by CART with Gini split criterion and evaluated by using 5-fold cross-validation. The produced decision tree model was based on NIHSS at admission, ischemic core volume and age features. The predictive accuracy of model was 86.5% and the AUC-ROC was 0.88. In conclusion, in this preliminary study we identified interpretable model based on clinical and neuroimaging features to predict clinical outcome in thrombolysis treated wake-up stroke patients.

Background: Efficiency of care chain response and hospital reactivity were and are challenged for stroke acute care management during the pandemic period of coronavirus disease 2019 (COVID-19) in North-Eastern Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige), counting 7,193,880 inhabitants (ISTAT), with consequences in acute treatment for patients with ischemic stroke., Methods: We conducted a retrospective data collection of patients admitted to stroke units eventually treated with thrombolysis and thrombectomy, ranging from January to May 2020 from the beginning to the end of the main first pandemic period of COVID-19 in Italy. The primary endpoint was the number of patients arriving to these stroke units, and secondary endpoints were the number of thrombolysis and/or thrombectomy. Chi-square analysis was used on all patients; furthermore, patients were divided into two cohorts (pre-lockdown and lockdown periods) and the Kruskal-Wallis test was used to test differences on admission and reperfusive therapies., Results: In total, 2536 patients were included in 22 centers. There was a significant decrease of admissions in April compared to January. Furthermore, we observed a significant decrease of thrombectomy during the lockdown period, while thrombolysis rate was unaffected in the same interval across all centers., Conclusions: Our study confirmed a decrease in admission rate of stroke patients in a large area of northern Italy during the lockdown period, especially during the first dramatic phase. Overall, there was no decrease in thrombolysis rate, confirming an effect of emergency care system for stroke patients. Instead, the significant decrease in thrombectomy rate during lockdown addresses some considerations of local and regional stroke networks during COVID-19 pandemic evolution., (© 2021. The Author(s).)

Background: A retrospective review of all patients admitted to a single vascular unit who underwent elective CEA between January, 2015 and December, 2019 was performed. The primary endpoints of the study were overall survival (from index operation) and cumulative stroke rate at thirty days. Patients and methods: A total of 383 consecutive patients were included in this study; of these 254 (66.4%) were males. At baseline, males were younger (mean age 73.4±11 vs. 76.3±10 years, p=.01) and with lower proportion of octogenarians (20.4% vs. 28.7%, p=.05). The rate of stroke in symptomatic and asymptomatic patients (males vs. females) were as follows: a) whole cohort 1.9% vs. 2% (p=1.00) and 2.7% vs. 1.3% (p=.66), respectively; b) ≥80 years old 3.7% vs. 0% (p=1.00) and 4% vs. 5.9% (p=1.00), respectively; c) <80 years old 1.2% vs. 3.3% (p=.47) and 2.5% vs. 0% (p=.55), respectively. The 3-year survival estimates were significantly lower for males (84% vs. 92%, p=.03). After stratification by age groups, males maintained inferior survival rates in the strata aged <80 years (85% vs. 97%, p=.005), while no differences were seen in the strata aged ≥80 years (82% vs. 79%, p=.92). Using multivariate Cox proportional hazards, age (HR: 2.1, 95% CI: 1.29-3.3, p=.002) and male gender (HR: 2.5, 95% CI: 1.16-5.5, p=.02) were associated with increased hazards of all-cause mortality. Results: A total of 383 consecutive patients were included in this study; of these 254 (66.4%) were males. At baseline, males were younger (mean age 73.4±11 vs. 76.3±10 years, p=.01) and with lower proportion of octogenarians (20.4% vs. 28.7%, p=.05). The rate of stroke in symptomatic and asymptomatic patients (males vs. females) were as follows: a) whole cohort 1.9% vs. 2% (p=1.00) and 2.7% vs. 1.3% (p=.66), respectively; b) ≥80 years old 3.7% vs. 0% (p=1.00) and 4% vs. 5.9% (p=1.00), respectively; c) <80 years old 1.2% vs. 3.3% (p=.47) and 2.5% vs. 0% (p=.55), respectively. The 3-year survival estimates were significantly lower for males (84% vs. 92%, p=.03). After stratification by age groups, males maintained inferior survival rates in the strata aged <80 years (85% vs. 97%, p=.005), while no differences were seen in the strata aged ≥80 years (82% vs. 79%, p=.92). Using multivariate Cox proportional hazards, age (HR: 2.1, 95% CI: 1.29-3.3, p=.002) and male gender (HR: 2.5, 95% CI: 1.16-5.5, p=.02) were associated with increased hazards of all-cause mortality. Conclusions: In this study of elective CEA for asymptomatic and symptomatic carotid stenosis, similar peri-operative neurologic outcomes were found in both males and females irrespective of age. Despite being usually older, females have superior long-term survival rates.

Background and Purpose: Diagnosis of posterior circulation stroke may be challenged. National Institutes of Health Stroke Scale (NIHSS) and brain imaging (non-contrast brain computed tomography-CT) are used for diagnosis; evaluation on posterior circulation stroke remains a limit of NIHSS, and the value of non-contrast CT (NCCT) is limited due to artifacts caused by the bones of the base of the skull. We tested the validity and prognostic value of posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) in patients with posterior circulation stroke., Methods: Pc-ASPECTS allots the posterior circulation 10 points. We studied 50 patients with posterior circulation stroke. We applied pc-ASPECTS to NCCT, CT angiography, and CT Perfusion. We evaluated the correlation of pc-ASPECT with outcome parameters for stroke., Results: Out of 50 patients, CTP showed abnormalities in 34 cases. The pc-ASPECT score calculated on brain CT and on the brain CT + angio CT had a sensibility of 24%, calculated on brain CT, angio CT and CTPerfusion gain a sensibility of 72%. Pc-ASPECT MTT resulted to be the more reliable parameter: outcome given by NIHSS score at discharge, mRS at discharge, and at 3 months was more severe in patients with Pc-ASPECT MTT alteration. Outcome given by NIHSS score at discharge and mRS at discharge and 1 at 3 months was more severe in patients with higher NIHSS score at admission., Conclusion: We evaluated the usefulness of pc-ASPECTS on CTP in predicting functional outcome in acute posterior circulation stroke that appears to be a powerful marker for predicting functional outcome., (© 2021. Fondazione Società Italiana di Neurologia.)

Purpose: The fear of COVID-19 infection may discourage patients from going to the hospital even in case of sudden onset of disabling symptoms. There is growing evidence of the reduction of stroke admissions and higher prevalence of severe clinical presentation. Yet, no studies have investigated the perfusion pattern of acute strokes admitted during the lockdown. We aimed to evaluate the effects of the COVID-19 pandemic on hyper-acute stroke CT perfusion (CTP) pattern during the first months of the pandemic in Italy., Methods: In this retrospective observational study, we analyzed CTP images and clinical data of ischemic stroke patients admitted between 9 March and 2 June 2020 that underwent CTP (n = 30), to compare ischemic volumes and clinical features with stroke patients admitted during the same period in 2019 (n = 51). In particular, CTP images were processed to calculate total hypoperfused volumes, core volumes, and mismatch. The final infarct volumes were calculated on follow-up CT., Results: Significantly higher total CTP hypoperfused volume (83.3 vs 18.5 ml, p = 0.003), core volume (27.8 vs 1.0 ml, p < 0.001), and unfavorable mismatch (0.51 vs 0.91, p < 0.001) were found during the COVID-19 period compared to no-COVID-19 one. The more unfavorable perfusion pattern at admission resulted in higher infarct volume on follow-up CT during COVID-19 (35.5 vs 3.0 ml, p < 0.001). During lockdown, a reduction of stroke admissions (- 37%) and a higher prevalence of severe clinical presentation (NIHSS ≥ 10; 53% vs 36%, p = 0.029) were observed., Conclusion: The results of CTP analysis provided a better insight in the higher prevalence of major severity stroke patients during the COVID-19 period., (© 2021. The Author(s).)

Background: When it comes to critical early post-acute TIA/stroke phase, there is a lack of a comprehensive multi-parametric telemonitoring system. The COVID-19 emergency, its related global mobility restrictions and fear of hospitalization further highlighted the need of a comprehensive solution., Objective: We aimed to design and test a pragmatic e-Health system based on multiparametric telemonitoring to support of TIA/stroke patients in sub-acute phase during the COVID-19 pandemic., Methods: We proposed a telemonitoring system and protocol for TIA/minor stroke patients during COVID-19 pandemic for patients at risk of stroke recurrence. This system involves the use of portable devices for BP/HR/SpO 2 /temperature sensing, panic-button, gateway, and a dedicated ICT platform. The protocol is a 14-day multiparametric telemonitoring, therapy, and emergency intervention based on vital sign alteration notifications. We conducted a proof-of-concept validation test on 8 TIA/minor stroke patients in the early post-acute phase (< 14 days from ischemic event)., Results: The proposed solution allowed to promptly and remotely identify vital sign alterations at home during the early post-acute phase, allowing therapy and behavioral intervention adjustments. Also, we observed a significant improvement of quality of life, as well as a significant reduction of anxiety and depression status. TUQ showed ease of use, good interface quality and high user satisfaction of the proposed solution. The 3-month follow-up showed total adherence of prescribed therapy and no stroke/TIA recurrence or other emergency department admissions., Conclusion: The proposed e-Health solution and telemonitoring protocol may be highly useful for early post-acute remote patient management, thus supporting constant monitoring and patient adherence to the treatment pathway, especially during the COVID-19 emergency., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Hypohydration may be associated with vascular diseases, poor prognosis and worse outcomes in stroke. The underlying mechanisms have not yet been completely investigated, although some studies suggested potential associations with brain perfusion and collaterals status. Despite the potentially different mechanisms promoting serum or urine biomarkers of hypohydration, few studies have investigated both markers separately. A prospective descriptive study was conducted in stroke patients admitted to a stroke unit <4.5 h from symptoms onset. All patients underwent neurological evaluation and whole-brain computed tomography perfusion (CTP) upon admission. Blood and urine samples were immediately collected at admission, and patients were defined as "hypohydrated" (HYP) if blood urea nitrogen-to-creatinine ratio was >15 and "underhydrated" (UND) if urine osmolality was >500 mOsm/kg. CTP images were processed to calculate core, penumbra, their mismatch and total hypoperfused volume. Forty-six patients were included and were grouped according to hydration status. Despite no different NIHSS at baseline, at CTP HYP was independently associated with core-penumbra mismatch (β: -0.157, 95% CI: -0.305 to -0.009; p = .04), while UND was independently associated with the total hypoperfused volume (β: 31.502, 95% CI: 8.522-54.481; p = .01). Using CTP imaging, this study proposes a physiological insight of some possible mechanisms associated with the better outcomes observed in acute stroke patients when properly hydrated. These results suggest different associations between hydration status and CTP parameters depending on serum or urine biomarkers in the hyper-acute phase and encourage the association between hydration status and stroke characteristics., (© 2021 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Background: Advanced neuroimaging can identify patients who can most benefit from reperfusion treatment, discriminating between ischemic core and penumbra area in a quick and accurate manner. Despite core-penumbra mismatch being an independent prognostic factor, computed tomography perfusion (CTP) assessment is still debated in hyperacute decision-making. The authors aimed to study a novel CTP mismatch score in emergency settings and to investigate its relation with clinical outcome in acute ischemic stroke patients treated with intravenous thrombolysis (IVT)., Methods: Neuroimaging and clinical data of 226 consecutive acute ischemic stroke patients were analyzed. The study population was divided into 5 different CTP scores: (0) without perfusion deficit, (1) only penumbra, (2) penumbra > core, (3) core ≥ penumbra, (4) only core. For differences in outcome between treated and nontreated patients, and among CTP core-penumbra groups to be assessed, the authors have evaluated the outcome in terms of National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) at discharge and symptomatic intracerebral hemorrhage., Results: A decrease in NIHSS was statistically greater in IVT-treated patients compared to nontreated patients showing only penumbra (ΔNIHSS%: 80.0% vs. 50.0%; P=0.0023) or no perfusion deficit (ΔNIHSS%: 89.4% vs. 61.5%; P=0.027) on CTP maps. The same trend was found in other groups without significant difference. A significant correlation was found in IVT patients between core/penumbra score and outcome in terms of ΔNIHSS (Kendall τ=-0.19; P=0.004)., Conclusions: The authors proposed a novel immediate CTP assessment to score perfusion mismatch in emergency settings to guide clinicians' decision-making for aggressive treatment and to prevent stroke-related disability., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Owing to the large inter-subject variability, early post-stroke prognosis is challenging, and objective biomarkers that can provide further prognostic information are still needed. The relation between quantitative EEG parameters in pre-thrombolysis hyper-acute phase and outcomes has still to be investigated. Hence, possible correlations between early EEG biomarkers, measured on bedside wireless EEG, and short-term/long-term functional and morphological outcomes were investigated in thrombolysis-treated strokes. EEG with a wireless device was performed in 20 patients with hyper-acute (< 4.5 h from onset) anterior ischemic stroke before reperfusion treatment. The correlations between outcome parameters (i.e., 7-day/12-month National Institutes of Health Stroke Scale NIHSS, 12-month modified Rankin Scale mRS, final infarct volume) and the pre-treatment EEG parameters were studied. Relative delta power and alpha power, delta/alpha (DAR), and (delta+theta)/(alpha+beta) (DTABR) ratios significantly correlated with NIHSS 7-day (rho = 0.80, - 0.81, 0.76, 0.75, respectively) and NIHSS 12-month (0.73, - 0.78, 0.74, 0.73, respectively), as well as with final infarct volume (0.75, - 0.70, 0.78, 0.62, respectively). A good outcome in terms of mRS ≤ 2 at 12 months was associated with DAR parameter (p = 0.008). The neurophysiological biomarkers obtained by non-invasive and portable technique as wireless EEG in the early pre-treatment phase may contribute as objective parameters to the short/long-term outcome prediction pivotal to better establish the treatment strategies.Graphical abstract Block diagram of study protocol and main findings. Assessment at admission including wireless EEG acquisition in emergency setting (< 4.5 from stroke onset), extracted EEG features before reperfusion thrombolytic treatment. The main findings in our study sample are summarized in two different exemplificative stroke patients with different pre-thrombolysis alterations of EEG parameters resulting in different final infarct volume extensions and short/long-term clinical outcomes (NIHSS, mRS).

Background: Migrainous aura (MA) represents the third most common stroke mimic (SM). Advanced neuroimaging is pivotal in the assessment of patients with focal neurological acute symptoms. We investigated brain perfusion alterations in MA-SM patients using a novel CT perfusion (CTP)-based quantitative approach in order to improve differential diagnosis between MA and acute stroke., Methods: We processed and analysed the clinical and neuroimaging CTP data, acquired within 4.5 h from symptom onset, of patients with acute focal neurological symptoms receiving a final diagnosis of MA. The differences between ROI, compatible with MA symptoms, and contralateral side were automatically estimated in terms of asymmetry index (AI%) by the newly developed tool for mean transit time (MTT), CBF, and cerebral blood volume (CBV) CTP parameters. The AI% ≥ 10% was considered significant., Results: Out of 923 admitted patients, 14 patients with MA were included. In 13 out of 14 cases, a significant pattern of hypoperfusion was observed by quantitative analysis in at least one of the CTP maps. In 7 patients, all three CTP maps were significantly altered. In particular, MTT-AI% increased in 11 (79%) cases, while CBF-AI% and CBV-AI% decreased in 12 (86%) and in 9 (64%) patients, respectively. All CBV values were above ischemic stroke core threshold and all MTT-AI were below ischemic penumbra threshold., Conclusions: Our data suggest that a novel CTP-quantitative approach may detect during MA a moderate hypoperfusion pattern in the cerebral regions compatible with aura symptoms. The use of this novel tool could support differential diagnosis between MA and acute stroke.

Purpose: Crossed cerebellar diaschisis (CCD) is a common finding in hyper-acute ischemic stroke, related to supratentorial dysfunction of the contralateral hemisphere. Several studies investigated a possible relationship between CCD and clinical outcomes but still no evidence emerged. We proposed a novel quantitative whole cerebellum analysis using CT perfusion (CTP) imaging to investigate the relationship between CCD and stroke severity, hypoperfused volume and outcome measures., Methods: 55 patients with supratentorial ischemic stroke who underwent CTP evaluation within 4.5 h since symptom onset were enrolled. CCD was evaluated by CTP image-processing and by calculating the mean transit time (MTT)-map asymmetry index in the whole cerebellum. MTT asymmetry correlation with ischemic volume and clinical outcomes was investigated., Results: MTT asymmetry was found in most of the included patients and significantly correlated with NIH Stroke Scale (NIHSS) score at baseline and CTP ischemic volume. MTT asymmetry was significantly correlated with hemorrhagic transformation, NIHSS and modified Rankin Scale (mRS) score on discharge in treated patients., Conclusions: CCD was detectable by CTP in acute supratentorial ischemic stroke by processing the whole cerebellum volume. CCD perfusion asymmetry was significantly correlated with neurological and perfusion deficit on admission as well as with clinical outcomes in treated patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The COVID-19 pandemics required several changes in stroke management and it may have influenced some clinical or functional characteristics. We aimed to evaluate the effects of the COVID-19 pandemics on stroke management during the first month of Italy lockdown. In addition, we described the emergency structured pathway adopted by an Italian University Hub Stroke Unit in the cross-border Italy-Slovenia area., Methods: We analyzed admitted patients' clinical features and outcomes between 9th March 2020 and 9th April 2020 (first month of lockdown), and compared them with patients admitted during the same period in 2019., Results: Total admissions experienced a reduction of 45% during the lockdown compared to the same period in 2019 (16 vs 29, respectively), as well as a higher prevalence of severe stroke (NIHSS>10) at admission (n = 8, 50% vs n = 8, 28%). A dramatic prevalence of stroke of unknown symptom onset was observed in 2020 (n = 8, 50% vs n = 3, 10%). During lockdown, worse functional and independence outcomes were found, despite the similar proportion of reperfused patients. Similar 'symptoms alert-to-admission' and 'door-to-treatment' times were observed. During lockdown hospitalization was shorter and fewer patients completed the stroke work-up., Conclusion: In conclusion, the adopted strategies for stroke management during the COVID-19 emergency have suggested being effective, while suffering a reduced and delayed reporting of symptoms. Therefore, we recommend raising awareness among the population against possible stroke symptoms onset. Thus, think F.A.S.T. and do not stay-at-home at all costs., Competing Interests: Declaration of Competing Interest The Authors declare that there is no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Backgrounds: Wake-Up Stroke (WUS) patients are generally excluded from thrombolytic therapy (rTPA) due to the unknown time of stroke onset. This study aimed to investigate the effects of rTPA in WUS patients during every day clinical scenarios, by measuring ischemic lesion volume and functional outcomes compared to non-treated WUS patients., Methods: We retrospectively analyzed clinical and imaging data of 149 (75 rTPA; 74 non-rTPA) patients with acute ischemic WUS. Ischemic volume was calculated on follow-up CT and functional outcomes were the NIHSS and mRS comparing rTPA and non-rTPA WUS. Patients were selected using ASPECTS > 6 on CT and/or ischemic penumbra > 50% of hypoperfused tissue on CTP., Results: A reduced volume was measured on the follow-up CT for rTPA (1 mL, 0-8) compared to the non-rTPA patients (10 mL, 0-40; p = 0.000). NIHSS at 7 days from admission was significantly lower in the rTPA (1, 0-4) compared to non-rTPA group (3, 1-9; p = 0.015), as was the percentage of improvement (ΔNIHSS) (70% vs 50%; p = 0.002). A higher prevalence of mRS 0-2 was observed in the rTPA compared to the non-rTPA (54% vs 39%; p = 0.060). Multivariate analysis showed that NIHSS at baseline and rTPA treatment are significant predictors of good outcome both in terms of NIHSS at 7 days and ischemic lesion volume on follow-up CT (p < 0.05)., Conclusions: rTPA in WUS patients selected with CT and/or CTP resulted in reduced ischemic infarct volume on follow-up CT and better functional outcome without increment of intracranial hemorrhages and in-hospital mortality.

Objective: The objective of the study was to review the current epidemiological evidence about the relationship between epilepsy and increased risk of cardio- and cerebrovascular events., Methods: We systematically searched MEDLINE (from inception to 19th October 2018) to identify population-based cohort studies evaluating the risk of subsequent stroke or myocardial infarction (MI) in patients with epilepsy without history of prior cerebrovascular disease in comparison with subjects without epilepsy., Results: A total of 16,641 records were screened, and 6 studies were included. Data on the risk of subsequent stroke and MI were provided by five and two studies, respectively. The adjusted hazard ratios ( adj HRs) of subsequent ischemic stroke for patients with epilepsy ranged from 1.09 (95% confidence interval (CI): 1.00-1.19) to 2.85 (95% CI: 2.49-3.26). Two studies assessing the incidence of hemorrhagic stroke showed an increased risk in patients with epilepsy ( adj HR: 3.30; 95% CI: 2.46-4.43 and adj HR: 2.27; 95% CI: 1.80-2.85). The adj HRs of subsequent MI ranged between 1.09 (95% CI: 1.00 to 1.19) and 1.48 (95% CI: 1.31-1.67). Age, hypertension, MI, diabetes, hyperlipidemia, and arteriosclerosis were significantly associated with the increase in stroke risk. A gradient between the antiepileptic drug (AED) dose and risk of subsequent stroke was found. In comparison with carbamazepine (CBZ), oxcarbazepine (OXC) was associated with an increased risk of stroke and valproate (VPA) with a reduction in risk of stroke and MI, whereas no significant associations with vascular disease were found for phenobarbital (PB), lamotrigine (LMT), phenytoin (PHT), clonazepam (CLZ), and clobazam (CLB)., Conclusions: Patients with epilepsy are at higher risk of subsequent stroke and MI in comparison with subjects without epilepsy. Although individual AEDs may carry different risks of cardio- and cerebrovascular disease, the clinical relevance of the metabolic effects of the enzyme-inducing AEDs is still uncertain. This article is part of the Special Issue "Seizures & Stroke"., Competing Interests: Declaration of Competing Interest No funding was received related to the preparation of this article. Francesco Brigo has received travel support from Eisai; he was one of the organizers of the “Seizures & Stroke” Congress, held in Gothenburg from 20th to 22nd February 2019. The remaining authors have no conflicts of interest to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Hypohydration has been suggested increasing the risk of vascular diseases, and it is associated with poor prognosis and worse functional outcome in stroke. Most studies have used blood parameters to determine patients' hydration status. The aim of this study was to measure urine osmolality (uOsm) and its influence on stroke severity and independence. A prospective descriptive study was conducted in stroke patients admitted to a stroke unit. All patients underwent neurological evaluation at admission and discharge using the National Institute of Health Stroke Scale (NIHSS). Independence at discharge was evaluated with the Barthel Index (BI) and the modified Rankin Scale (mRS). uOsm was measured at admission. Patients were grouped in "poor fluid intake" (PF) and "euhydration" (EU), the latter if uOsm ≤ 500 mOsm/kg. Among 119 included patients, the prevalence of PF was 52%, with no difference observed between groups in demographics or blood samples analyses. PF had higher chances of NIHSS > 8 at admission (OR: 4.7 95% CI: 1.3-17.0; p = 0.02), lower BI at discharge (β: -15.3 95% CI: -26.7 to -3.8; p = 0.01), and worse mRS at discharge (OR: 4.01 95% CI: 1.2-14.0; p = 0.02). These findings are consistent with previous results, suggesting that uOsm may be a factor significantly associated with stroke severity and independence outcome after acute ischemic stroke., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest for this study, and this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. ACQUA@BRAIN was part of the standard care of the ASUITs stroke unit and was supported by regional fundings for quality improvement., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Recombinant tissue plasminogen activator (rt-PA) is the first-line therapy demonstrated to be safe and effective in acute ischemic stroke. People with pre-existing severe dementia or physical disability are usually excluded from rt-PA. The aim of our study was to investigate rt-PA safety and effectiveness in acute stroke with pre-existing disability (mRS ≥ 2)., Methods: The study encompassed 35 acute ischemic stroke patients with mRS ≥ 2 treated with rt-PA. In order to assess the differences in clinical outcome in three disability groups (mRS = 2; 3; 4/5), the following parameters were evaluated: intracerebral hemorrhage, mortality, NIHSS, ΔNIHSS and mRS., Results: Baseline-NIHSS and age were not significantly different among groups. Mortality was higher in the pre-morbid mRS 4/5 group (44%) than in the pre-morbid mRS2 (16.7%) and mRS 3 groups (21.4%). In survived patients, median ΔNIHSS% was higher in the mRS2 and 3 groups (-63.3% and -92.3%, respectively) than in the mRS4/5 group (-9.1%). The 247 rt-PA treated subjects with mRS < 2 in the same period showed lower mortality rate (4.7%), lower sICH (5%), lower mRS at discharge (median 1; range 0-6) and similar ΔNIHSS% (-75%)., Conclusion: Patients with mRS 2 and 3 may benefit from rt-PA with a moderate risk of sICH and mortality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Care partners of stroke survivors are often characterized by high burden levels and depression. Passive and active interventions have been proposed to help reduce burden and depression. The aim of this quality improvement report was to evaluate the effects of a single passive intervention on reported burden and depression in carers of stroke survivors., Methods: A quality improvement report was conducted on carers who participated in a short passive intervention (n = 56) and a control group (n = 44). The Family Strain Questionnaire-Short Form (FSQ-SF) and the Beck Depression Inventory II were administered in both groups at patients' admission and before discharge, with the intervention taking place between the 2 data collection periods., Results: No significant difference between groups was observed in FSQ-SF score and prevalence of depression at admission and in FSQ-SF at discharge. However, compared with admission, FSQ-SF at discharge was significantly reduced only in the intervention group (pre: 14, and interquartile range, 12-15; post: 9, and interquartile range, 9-13; P < .01). Moreover, a smaller proportion of carers classified as "depression" was found at discharge in the intervention group compared with controls (4% vs 28%, respectively; P < .01)., Conclusion: Results encourage the development and use of short passive intervention to reduce burden and depression in care partners of stroke survivors.

Introduction: Thrombolysis may affect ischemic stroke-related size, pattern and nature of infarcts, and has the potential to change aphasia presentation and recovery. Data on evolution of post-stroke aphasia following thrombolysis are still scarce. The aim of this study was to determine the course of language recovery through a well-validated language assessment battery after acute ischemic stroke and investigate whether traditional categorical classifications of aphasia can describe the clinical picture in post-thrombolysis phase., Materials and Methods: Demographic, clinical, and language assessment data of 116 patients presenting sub-acute ischemic stroke aphasia (41 treated with r-tPA; 75 non-treated) were retrospectively analyzed. The participants were assessed by a clinical neuropsychologist with a variety of subtests taken from a well-validated Italian language battery (Neuro-Psychological Aphasia Evaluation)., Results: The percentage of resolved aphasia was significantly higher in treated patients compared to non-treated patients (p = 0.005) and global aphasia was more common in the non-treated group (non-treated 30.7% vs treated 17.1%). Aphasia subtypes and stroke etiologies showed no significant association, except for small vessel etiology and resolved aphasia (p = 0.041). Reperfusion treatment, baseline NIHSS, and lacunar stroke were the predictors of aphasia recovery., Conclusion: The percentage of resolved aphasia was significantly higher in the treated patients compared to the non-treated, with the latter showing a higher percentage of global aphasia. Identifying classic aphasia subtypes after thrombolysis is still possible since reperfused areas do not necessary change the classification or lead to completely different aphasic syndromes. Reperfusion treatment, baseline NIHSS, and lacunar stroke were the main predictors of aphasia recovery., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: The combined use of perfusion neuroimaging and brain oscillatory activity may provide a better clinical picture of neurovascular coupling of the injured area in ischemic stroke. The aim is to assess stroke-related topographic electroencephalography (EEG) changes during the earliest phase of ischemic stroke and to compare them with hypoperfusion identified by computer tomography perfusion (CTP)., Patients and Methods: The study included 15 patients with ischemic stroke, who underwent both CTP and EEG recording within 4.5 h. Topographic representation of power for each band was calculated and compared with hypoperfusion areas estimated by CTP maps., Results: Predominance of slow delta frequencies was found in all patients. The main finding is the agreement between slow rhythms hemispheric prevalence on EEG maps and cerebral hypoperfusion area identified using CTP., Conclusion: The results of this preliminary study show that the combined use of EEG and CTP, as highly available techniques, in acute ischemic stroke may be helpful in clinical practice and provide information about functional and metabolic aspects of brain involvement. The joint use of these methodologies may give a better clinical insight of the functionality of injured area in the hyperacute phase., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Isolated speech impairment is one of the most challenging clinical manifestations of stroke mimic (SM). We aimed to investigate perfusional and EEG pattern of isolated aphasia to better differentiate between vascular and epileptic etiology in emergency settings., Method: We retrospectively analyzed 481 cases with acute focal neurological symptoms admitted to our Stroke Unit. The patients showing isolated aphasia and confirmed ischemic infarction or SM with seizure etiology on follow-up were included for subsequent analysis of clinical, neuroimaging, and EEG data. We investigated differences in CT Perfusion maps between ROI in the anatomical area compatible with clinical presentation, contralateral ROI and EEG in order to evaluate perfusion and brain oscillatory activity abnormalities., Results: 45 patients presented isolated aphasia as principal neurological symptom: 27 cases due to acute ischemic event, 11 due to seizure SM, while 7 were SM due to other etiologies. Out of 11 SM patients with seizure etiology, significant hyperperfusion on CTP maps (MTT AI%<-10%) and sharp EEG waves were observed in 8 patients, while in 3 patients slight hypoperfusion (MTT AI%<20%) and slow EEG rhythms were detected. 24 out of 27 ischemic stroke patients presented severe hypoperfusion with MTT AI above the stroke threshold (MTT AI > 45%). All ischemic stroke patients presented slower EEG rhythms., Conclusions: The main finding of this study is the identification of different clinical and neuroimaging patterns of isolated aphasia with epileptic or ischemic etiology in emergency settings., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Introduction: Stroke mimics (SM) account for 1% to 41% of all AIS presentation. Seizures are the most frequent cause of mimic, but isolated speech impairment, among adult-onset epilepsy, is quite rare, while aphasia is more often due to an AIS. Prompt AIS/SM recognition is required to establish the most appropriate therapeutic management. We aimed at identifying some predictive clinical and anamnestic features useful to differentiate SM from AIS, particularly in patients presenting with aphasia., Materials and Methods: A retrospective study of patients admitted for a suspected stroke, from January 2015 until January 2017 was performed. We identified patients discharged with a final diagnosis of aphasia and patients with seizures presenting with speech impairment. Anamnestic, clinical and diagnostic were reviewed. Univariate analyses determined key clinical features predictive of AIS versus an epileptic SM., Results: 72 patients with sudden onset of aphasia were identified. A cerebrovascular etiology was diagnosed in 50 patients while an epileptic SM in 22. The presence of ischemic cardiopathy, atrial fibrillation and mild lateralizing signs were strongly suggestive of stroke. Otherwise, a previous history of epilepsy, alteration of consciousness, concomitant infection and electrolyte imbalance were predictors of a SM., Conclusions: Our study underscores the importance of an accurate clinical bed-side assessment as the first step in the diagnostic and therapeutic decision-making process for patients presenting with aphasia. The detection of clinical and anamnestic features associated with an epileptic SM could be useful for the diagnostic process and for time-critical treatments., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Intravenous thrombolysis within 4.5 hours from symptom onset improves functional outcome in acute ischemic stroke patients. Repeated intravenous tissue plasminogen activator (IVtPA) is contraindicated in patients presenting with early recurrent stroke (ERS) within 3 months from the initial stroke because of a greater risk of intracranial hemorrhage., Case Presentation: A 59-year-old man presented with ERS, National Institute of Health Stroke Scale of 16, 10 days after a previous stroke. Brain computed tomography (CT) showed a previous hypodensity with 4 cm volume. Angio-CT highlighted the left middle cerebral artery and left internal carotid occlusion. Perfusion CT showed small deep core and large penumbra. The patient underwent IVtPA. After 24 hours, the National Institute of Health Stroke Scale was 7, and CT scan showed an acute ischemic lesion in the left basal ganglia area and frontal lobe without hemorrhagic transformation., Conclusion: This case report suggests that further randomized studies may evaluate whether repeated IVtPA may be safe and effective in ERS occurring shortly after a previous stroke when patients experience a period of complete neurological regression, minor disability, and a small infarct volume. Should the hypothesis be confirmed, small volume core and wide volume penumbra at perfusion CT may support the decision of adopting IVtPA repetition.

Proper hydration and nutrition have been found to be contributing factors to a better recovery in patients after stroke. A better knowledge of factors influencing fluid and energy intake may contribute to a better care of the acute stroke patient. Aim of this study was to describe hydration status, fluid intake, and energy intake of stroke patients during acute hospitalization in a stroke unit. A retrospective descriptive study was conducted in stroke patients admitted to a stroke unit. All patients received neurological evaluation and urinary osmolality (uOsm) measure at admission and discharge. During stroke unit stay patients received a day-by-day diary to record data about beverages, food, and therapy. Water and energy content were then reported based on a national nutritional database. Ninety-five patients were included in the analysis. uOsm did not differ between patients with or without dysphagia, with uOsm > 500 mosm/kg in 58.1% at admission and 57.8% at discharge. Inadequate fluid intake was found in 41.2% of the sample with no difference between groups. Insufficient energy intake was found in 95.6% of the sample, with no patients with dysphagia reaching the minimum suggested amount. Our results suggest that a relevant proportion of stroke patients with and without dysphagia may not improve their hydration status during the first days after admission. Diet and therapy were insufficient to achieve recommended fluid intake and energy intake in a large proportion of patients, suggesting a more careful monitoring of hydration and nutrition needs., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Ischemic stroke is a neuroemergency condition highly treatable with thrombolysis and thrombectomy. Recently, observational studies have brought insights into clinical and imaging characteristics of wake-up stroke, which interested up to 25% of ischemic stroke patients. In clinical practice, wake-up strokes are usually not considered for reperfusion therapy. The aim of this study was to investigate the use CT perfusion imaging in patients with wake-up stroke and to assess the effect of neuroimaging information provided by CT perfusion maps on the efficacy and safety of thrombolysis and thrombectomy., Patients and Method: We studied 22 wake-up stroke (WUS) patients (13F/9M mean age) who underwent reperfusion therapy after the eligibility assessed by the CT perfusion imaging (< 50% core-to-penumbra ratio and negative CT perfusion)., Results: Mean National Institutes of Health Stroke Scale (NIHSS) was 8.1 ± 4.9 at admission while 3.3 ± 5.1 at discharge, significantly different from admission (p < 0.001). As many as ten patients had mRS lower than 3 at discharge. Intracranial hemorrhage occurred in five patients and caused symptoms worsening only in two patients (decrease of NIHSS score of 4 points) of which one patient died., Conclusion: The main finding of this study is that wake-up stroke with adequate selection by CT perfusion may benefit reperfusion treatment.

Background: The National Institutes of Health Stroke Scale (NIHSS) is the most adopted stroke patients' evaluation tool in emergency settings to assess the severity of stroke and to determine the patients' eligibility for specific treatments. Computed tomography perfusion (CTP) is crucial to identify salvageable tissue that can benefit from the reperfusion treatment. The aim of this study is to identify the relation between the NIHSS scores and the hypoperfused volumes evaluated by CTP in patients with hyperacute ischemic stroke., Methods: This retrospective study was conducted on 105 patients with ischemic stroke who underwent NIHSS assessment and CTP in the hyperacute phase. Hypoperfused volume was evaluated by CTP maps processed with semi-automatic algorithm. An analysis was conducted to determine the degree of correlation between the NIHSS scores and the ischemic lesion volumes and to investigate the relation between the anterior and the posterior circulation strokes, as well as between the right and the left hemispheric strokes., Results: A significant correlation was found between ischemic volume and NIHSS score at baseline (r = .82; P < .0001) in the entire cohort. A high NIHSS-volume correlation was identified in the anterior circulation stroke (r = .76; P < .0001); whereas, it was nonsignificant in the posterior circulation stroke. NIHSS score and volume correlated for the left and the right hemispheric strokes (r = .83 and .81; P < .0001), showing a slightly higher slope in the left., Conclusion: This study showed a strong correlation between the baseline NIHSS score and the ischemic volume estimated by CTP. We confirmed that NIHSS is a reliable predictor of perfusion deficits in acute ischemic stroke. CTP allows fast imaging assessment in the hyperacute phase. The results highlight the importance of these diagnostic tools in the assessment of stroke severity and in acute decision-making., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Bilateral arm training (BAT) has shown promise in expediting progress toward upper limb recovery in chronic stroke patients, but its neural correlates are poorly understood., Objective: To evaluate changes in upper limb function and EEG power after a robot-assisted BAT in chronic stroke patients., Methods: In a within-subject design, seven right-handed chronic stroke patients with upper limb paresis received 21 sessions (3 days/week) of the robot-assisted BAT. The outcomes were changes in score on the upper limb section of the Fugl-Meyer assessment (FM), Motricity Index (MI), and Modified Ashworth Scale (MAS) evaluated at the baseline (T 0 ), posttraining (T 1 ), and 1-month follow-up (T 2 ). Event-related desynchronization/synchronization were calculated in the upper alpha and the beta frequency ranges., Results: Significant improvement in all outcomes was measured over the course of the study. Changes in FM were significant at T 2 , and in MAS at T 1 and T 2 . After training, desynchronization on the ipsilesional sensorimotor areas increased during passive and active movement, as compared with T 0 ., Conclusions: A repetitive robotic-assisted BAT program may improve upper limb motor function and reduce spasticity in the chronically impaired paretic arm. Effects on spasticity were associated with EEG changes over the ipsilesional sensorimotor network.

Objectives: The acute-onset of migrainuos aura (MA) can be erroneously diagnosed in Emergency Department (ED) as acute stroke (AS) and it can be classified as "stroke mimic" (SM). Perfusion computer tomography (PCT) may be useful to improve detection of infarcts. The aim of the study was to investigate the role in ED of PCT in improving diagnosis of migrainous aura. Data were compared with the well-defined perfusion patterns in patients with acute ischemic stroke., Patients and Methods: A standardized Stroke Protocol was planned. The protocol consisted in centralizing in ED all the patients with acute-onset of neurological symptoms compatible with cerebrovascular disease and in performing a general and neurological examination, hematological tests, brain non-contrast computed tomography (NCCT), CT angiography (CTA) of the supra-aortic and intracranial arteries and cerebral PCT. Patients with diagnosis of definite or probable acute stroke were hospitalized in Stroke Unit (SU). A six-months retrospective analysis of all the patients included in the Stroke Protocol and discharged from ED or from SU with a diagnosis of migraine with aura was performed., Results: 172 patients were included in the Stroke Protocol and 6 patients were enrolled. NCCT, CTA and PCT were performed after 60-90 min from symptoms onset and revealed normal perfusion. Intravenous thrombolysis was performed only in one patient., Conclusion: Patients with acute-onset of neurological symptoms, who have rapid progressive improvement of symptoms, normal neuroimaging, in particular PCT, and preceding episodes of migraine with aura, may be considered as suffering from MA. In these cases, even if thrombolysis is safe, clinicians may defer a prompt aggressive treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Different transcranial direct current stimulation (tDCS) paradigms have been implemented to treat poststroke spasticity, but discordant results have been reported., Objective: This study aimed to determine the efficacy and persistence of dual tDCS (anode over affected motor cortex [M1] and cathode over contralateral M1) compared with cathodal tDCS (cathode over contralateral M1) on upper limb (UL) functional, behavioral, and neurophysiological measures in chronic poststroke individuals., Subjects and Methods: Ten subjects with UL spasticity (7 men; mean 62 years; 8 ischemic stroke; years from event: 2.3 years) were enrolled in a cross-over, double-blinded study. Cathodal and dual tDCS, both preceded by 1 week of sham stimulation 1 month before real stimulation, were applied with 3 months interval. Stimulating paradigm was 20 minutes for five consecutive days in each block. Evaluations were performed before (T1), after real or sham treatment (T2), and after 1 (T3), 4 (T4), and 8 weeks (T5). Functional, behavioral, and neurophysiological tests were performed at each time., Results: Both tDCS paradigms decreased spasticity, increased strength, and ameliorated behavioral scales. Cathodal tDCS was superior to dual tDCS in reducing UL distal spasticity immediately after treatment (T2: cathodal > dual: P = .023) and provided a higher and longer lasting reduction at proximal districts (T3: cathodal > dual: P = .042; T4: cathodal > dual: P = .028; T5: cathodal > dual: P = .05). These findings are supported by an H-reflex modulation (overall time effect P > .002)., Conclusions: Cathodal tDCS is slightly more effective than dual tDCS in reducing distal UL spasticity in chronic poststroke subjects. A modulation of spinal inhibitory mechanisms, demonstrated by H-reflex modifications, supports this finding., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective: Stroke is one of the leading causes of disability and death in the world. The endocannabinoid (eCB) system is upregulated in several neurological diseases including stroke. A previous animal study demonstrated an increased expression of the endocannabinoid receptor 1 (CB1R) in the penumbra area surrounding the ischemic core, suggesting a crucial role in inflammation/reperfusion after stroke. Regarding the localization of CB1/CB2 receptors, animal studies showed that cortical neurons, activated microglia, and astroglia are involved. Our aim was to evaluate the cerebral expression of CB1R in the ischemic brain areas of 9 patients who died due to acute cerebral infarction in the middle cerebral artery territory., Methods: The cerebral autoptic tissue was collected within 48 hours since death. Ischemic and contralateral normal-appearing areas were identified. After tissue preprocessing, 4-µm-thick cerebral sections were incubated with the primary CB1R antibodies (Cayman Chemical Company, Ann Arbor, MI). Thereafter, all cerebral sections were hematoxylin treated. In each section, the total cell number and CB1R-positive cells were counted and the CB1R-positive cell count ratio was calculated. For statistical analysis, Student's t-test was used., Results: In normal tissue, CB1R-positive neurons were the majority; a few non-neuronal cells expressed CB1R. In the ischemic areas, a few neurons were detectable. A significant increase in total CB1R staining was found in the ischemic regions compared to contralateral areas., Conclusions: We found an increase in CB1R expression in the ischemic region (neuronal and non-neuronal cell staining), suggesting the inflammatory reaction to the ischemic insult. Whether such response might mediate neuroprotective actions or excitotoxicity-related detrimental effects is still unclear., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The development of an innovative functional assessment procedure based on the combination of electroencephalography (EEG) and robot-assisted upper limb devices may provide new insights into the dynamics of cortical reorganization promoted by rehabilitation. The aim of this study was to evaluate changes in event-related synchronization/desynchronization (ERS/ERD) in alpha and beta bands in a patient with pure sensory stroke who underwent a specific rehabilitation program for somatic sensation recovery. A 49-year-old, right-handed woman (time since stroke, 12 months) with severe upper limb somatic sensation deficits was tested using validated clinical scales and a standardized video-EEG system combined with the Bi-Manu-Track robot-assisted arm trainer protocol. The patient underwent a 3-month home-based rehabilitation program for promoting upper limb recovery (1 hour a day for 5 days a week). She was tested before treatment, at 1-month, and at 3-month during treatment. Results showed progressive recovery of upper limb function over time. These effects were associated with specific changes in the modulation of alpha and beta event-related synchronization/desynchronization. This unique study provides new perspectives for the assessment of functional deficits and changes in cortical activity promoted by rehabilitation in poststroke patients., (© EEG and Clinical Neuroscience Society (ECNS) 2014.)

Rehabilitation programs, to be efficiently tailored, need clear prognostic markers. In acute stroke, neurophysiological measures, such as motor evoked potentials (MEPs), have been proposed, although with discordant results. The aim of this study was to identify a reliable neurophysiological measure of recovery in acute post-stroke individuals by combining MEPs and the N100 component of transcranial magnetic stimulation-evoked potentials (TEPs). Nine acute post-stroke subjects were included. Clinical evaluation performed in the first week after the event included administration of the European Stroke Scale and Barthel Index and recording of MEPs and TEPs; administration of the clinical scales was repeated after one and three months. The presence/absence of MEPs and TEPs showed correlations with motor outcome. Individuals with a poorer outcome showed absence of both MEPs and TEPs; absence of MEPs alone was related to a partial recovery. Given the results of this exploratory study, further investigation is needed to define the accuracy of combined use of MEPs and TEPs as an approach for predicting motor recovery after acute stroke.

Objectives: To assess the use of extracorporeal shock wave therapy (ESWT) for the treatment of equinus foot after stroke and to correlate the ESWT effect on spastic plantar-flexor muscles with echo intensity on the Heckmatt scale., Methods: The prospective open-label study examined 23 patients with poststroke lower limb spasticity. Adults with spastic equinus foot after stroke received one ESWT session on hypertonic plantar-flexor muscles. The effect on spasticity, degree of passive ankle dorsiflexion, and neurophysiological values were evaluated. Before treatment, participants underwent a sonography evaluation of calf muscles to identify echo intensity on the Heckmatt scale., Results: Immediately after the session, ESWT induced a statistically significant reduction in muscle tone, increasing passive ankle dorsiflexion motion. At 30 days of follow-up, the effect persisted only in patients with echo intensity of spastic plantar-flexor muscles graded I, II, or III on the Heckmatt scale without any action related to spinal excitability. Mild adverse events were reported after the treatment but were resolved in a few days., Conclusions: ESWT is safe and efficacious for the treatment of poststroke plantar-flexor muscles spasticity, reducing muscle tone and improving passive ankle dorsiflexion motion. The effect was long lasting in subjects with echo intensity of calf muscles graded I, II, or III but was brief for echo intensity graded IV on the Heckmatt scale. The ESWT effect did not appear to be related to spinal excitability.

Stroke leaves many patients disabled even after rehabilitative training, representing a major cause of disability. Several approaches to improve outcomes have been attempted in recent years, with only relative benefit. Emerging evidences show a potential role of pharmacological intervention to enhance motor recovery after stroke. Contrasting evidence are coming from experimental and clinical studies, so far, and pharmacological intervention during rehabilitation represents a major controversial in neurorehabilitation. Dopaminergic stimulation appears as one of the most promising way to improve motor recovery. Subject of this paper will be the ratio underlying the clinical use of levodopa in chronic stroke patients, trying to outline the most convincing evidences about a potential role of this drug in rehabilitative strategies.

Research is on-going to identify new methods of biostimulation to increase the effect of botulinum toxin type A (BTX-A) in the treatment of spasticity. The Spasticity treated by Botulinum Toxin and ESWT (SBOTE) study is a prospective, randomized controlled trial assessing the effectiveness of extracorporeal shock wave therapy (ESWT) given immediately after BTX-A injections compared with electrical stimulation (ES) given immediately after BTX-A therapy for the management of focal upper limb spasticity in stroke patients. ES was given for 30 min twice a day for 5 days starting at 5 Hz; ESWT was given once a day for 5 days. At study follow-up, patients treated with BTX-A injections and ESWT showed a statistically greater significance and continuous decrease of spasticity measure (modified Ashworth scale [MAS]: 1.37, 1.75 and 1.58 at 15, 30 and 90 days post-treatment, respectively), of spasms (spasm frequency scale [SFS]: 0.8 and 0.25 at 30 and 90 days post-treatment, respectively) and of pain (visual analogue scale [VAS]: 1.94 and 1.87 at 30 and 90 days, respectively) compared with patients treated with BTX-A injections and ES (MAS: 2.37, 2.18 and 2.18, respectively) (p < 0.05) (SFS: 1.5 and 1.06, respectively) (p < 0.05) (VAS: 2.44 and 2.69 respectively) (p < 0.05). ESWT enhances the effect of BTX-A to a greater extent than ES, probably by modulating rheology of the muscle and neurotransmission at the neuromuscular junction., (Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate blood oxygenation level-dependent (BOLD) activation during somatosensory electrical stimulation of the median nerve in acute stroke patients and to determine its correlation with ischemic damage and clinical recovery over time., Methods: Fourteen acute stroke patients underwent functional magnetic resonance imaging (fMRI) during contralesional median-nerve electrical stimulation 12-48 h after stroke. Findings were then validated by diffusion tensor imaging (DTI) and motor evoked potential by transcranial magnetic stimulation (TMS)., Results: Poor clinical recovery at three months was noted in four patients with no activation in the early days after stroke, whereas good clinical recovery was observed in eight patients with a normal activation pattern in the primary sensory motor area in the acute phase. In two patients BOLD activation correlated weakly with clinical recovery. Findings from TMS and DTI partially correlated with clinical recovery and functional scores., Conclusions: Clinically relevant insights into the "functional reserve" of stroke patients gained with peripheral nerve stimulation during fMRI may carry prognostic value already in the acute period of a cerebrovascular accident., Significance: BOLD activation maps could provide insights into the functional organization of the residual systems and could contribute to medical decision making in neurological and rehabilitative treatment., (Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Motor excitability is increased in both hemispheres in stroke patients during motor recovery. Pharmacologically controlled changes of cortical excitability might be beneficial for synaptic plasticity and therefore facilitate functional recovery after a brain lesion. In particular, it has been suggested that antidepressant drugs can modulate motor excitability. Several recent reports suggest the possibility of monitoring pharmacological effects on brain excitability through transcranial magnetic stimulation (TMS). The aim of this study was to investigate motor area excitability in patients with stroke after oral administration of citalopram. We conducted a prospective randomised placebo controlled study. Twenty patients with unilateral stroke were included in the study: ten patients treated by antidepressive drug and ten patients with placebo. A selective serotonergic drug (citalopram) or a placebo was administered using a mean dosage of 10 mg/day in combination with physiotherapy. Motor cortex excitability was studied by single and paired transcranial magnetic stimulation. TMS recording was tested before (T1) and 1 month after (T2) beginning drug treatment. Patients treated by the serotonergic drug, compared to patients that received a placebo, showed a significant improvement in neurological status as measured by NIHSS and a decrease of motor excitability over the unaffected hemisphere, while no differences were observed over the affected hemisphere. Our findings suggest that treatment with serotonergic drugs can bring about a significant decrease of the motor cortex excitability in stroke patients with effects on both the affected and unaffected hemispheres associated with a better motor recovery.

Purpose: Promising new rehabilitative approaches to improve the substantial motor disability associated with chronic stroke include pharmacotherapy to enhance motor recovery. We conducted a single-blind placebo-controlled crossover pilot study to investigate the effects of prolonged treatment with L-DOPA in stroke patients., Methods: Ten chronic (10-48 months) stroke patients received placebo or L-DOPA 100 mg daily for 5 weeks. During drug's treatment patients suspended physiotherapy. Patients underwent clinical evaluation (Rivermead Motor Assessment, Nine Hole Peg Test, and 10 meter walking test) and transcranial magnetic stimulation recordings from the affected and unaffected hemisphere (resting motor threshold, motor evoked potential amplitude and cortical silent period) before and after 5 weeks of treatment., Results: After L-DOPA treatment patients improved their walking speed (p < 0.01) and manual dexterity ( p < 0.01) with the affected hand, the cortical silent period over the affected hemisphere lengthened (p < 0.01), while no changes were found in placebo-group., Conclusion: A 5-week course of oral L-DOPA in a single daily dose substantially improves motor performance in patients with chronic stroke and could do so by modulating motor cortical excitability (cortical silent period lengthening) suggesting that cortical inhibitory mechanisms have a role in motor recovery after stroke. Pharmacotherapy could be a useful therapeutic approach for chronic stroke patients.

Background: Functional neuroimaging studies show adaptive changes in areas adjacent and distant from the stroke. This longitudinal study assessed whether changes in cortical excitability in affected and unaffected motor areas after acute stroke correlates with functional and motor recovery., Methods: We studied 13 patients with moderate to severe hemiparesis 5 to 7 days (T1), 30 days (T2), and 90 days (T3) after acute unilateral stroke, as well as 10 healthy controls. We used paired-pulse transcranial magnetic stimulation to study intracortical inhibition and facilitation, recording from the bilateral thenar eminences. F waves were also recorded., Results: At T1, all patients showed significantly reduced intracortical inhibition in the unaffected hemisphere. At T2, in patients whose motor function recovered, intracortical inhibition in the unaffected hemisphere returned to normal. In patients with poor clinical motor recovery, abnormal disinhibition persisted in both hemispheres. At T3, in patients whose motor function progressively recovered, the abnormal disinhibition in the unaffected hemisphere decreased further, whereas in patients whose motor function remained poor, abnormal inhibition in the unaffected hemisphere persisted. No modification of F-wave latency and amplitude were found in patients and controls., Conclusions: During early days after stroke, motor cortical disinhibition involves both cerebral hemispheres. Longitudinal changes in motor disinhibition of the unaffected hemisphere may reflect the degree of clinical motor recovery.

Optimal treatment of spasticity requires a combination of pharmacotherapy and muscle lengthening. We evaluated 13 stroke patients with equinovarus foot randomized to treatment with either botulinum toxin A (BTA) injection plus ankle-foot casting (n=6) or BTA alone (n=7). The tibialis posterior and calf muscles (range of BTA injection: 190 to 320 U) were treated in each patient. Castings were worn at night for four months. Each patient was examined before, and at two and four months after BTA injection using the static and dynamic baropodometric tests, the Modified Ashworth Scale and the 10-meter walking test. At two months, therapeutic effects were observed in both groups. At four months, the study group showed further clinical improvement, while the control group returned to baseline performance. Thus, prolonged stretching of spastic muscles after BTA injection affords long-lasting therapeutic benefit, enhancing the effects of the toxin alone.