In deaths and diseases attributed to tobacco smoke cardiovascular events exceed cancer and respiratory diseases. Second hand smoke (SHS) promotes the development of arteriosclerosis and can also trigger acute changes of endothelial function and of blood coagulability. Indoor smoking bans reduced coronary syndrome and myocardial infarction 10-20% within one year and were followed by sustainable decreases of stroke and diabetes. With a smoke-free hospitality industry people recognized tobacco smoke as an air pollutant, smoking in public was denormalized and social acceptance of smoking in front of children and pregnant women decreased also in homes and in cars. Combined effects with ambient air pollution are proven for active smoking and suspected for SHS. Contamination with third hand smoke (THS, “cold smoke”) persists for months in homes and cars, creating secondary pollutants that in some cases are more toxic (e.g., tobacco-specific nitrosamines). Remnants found in air, dust, and on surfaces (carpets, wallpapers, upholstery, soft toys) were associated with their metabolites in saliva and urine of children and with elevated levels of nicotine on hands and cotinine in urine of nonsmokers residing in homes previously occupied by smokers. In animal experiments effects of THS were found on thrombogenesis, insulin resistance through oxidative stress, on the developing immune system, lipid metabolism and alterations in liver, lung, skin and behavior. Much less is known about health effects for bystanders from the aerosols exhaled during “vaping” of e-cigarettes, but nicotine and other toxins from e-cigarettes are certainly a hazard, which should be prevented by the use of dermal and oral nicotine products, which are safer for nicotine replacement and without risk for bystanders.

Objective: to evaluate the effects of excitatory repetitive transcranial magnetic stimulation (rTMS) of the international 10-20 system P3 point (intraparietal sulcus region) in chronic patients with a frontal lesion and parietal sparing due to stroke on the impaired upper (UL) and lower limb (LL) as measured by Fugl-Meyer Assessment (FMA). Methods: three patients (C1: 49.83/2.75, C2: 53.17/3.83, C3: 63.33/3.08 years-old at stroke/ years post-stroke, respectively) received two weeks (five days/ week) of rTMS at 10 Hz of P3. A patient was treated in similar conditions with a sham coil (S1: 56.58/4.33). No complimentary therapy was delivered during the study. Patients were evaluated before, after- and two months post-treatment (A1, A2 and A3, respectively). Results: we found increased scores for LL in motor function subsection for C1 and C3 and in sensory function for C2 by A2 that remained at A3. We also found an increased score for UL motor function for C2 and C3, but the score decreased by A3 for C2. C3 score for UL range of motion increased by A3 compared to A1 and A2. Conclusion: In a variable way, P3 excitatory rTMS increased FMA scores in different upper and lower limb subsections of our three treated patients.

The Coronavirus disease due to SARS-CoV-2 emerged in Wuhan city, China in December 2019 and rapidly spread more than 200 countries as a global health pandemic. There are more 3 million confirmed cases and around 207,000 fatalities. The primary manifestation is respiratory and cardiac but neurological manifestations are being reported in the literature as case reports and case series. The most common reported symptoms to include headache and dizziness followed by encephalopathy and delirium. Among the complications noted are Cerebrovascular accident, Guillian barre syndrome, acute transverse myelitis, and acute encephalitis. The most common peripheral manifestation was hyposmia. It is further noted that sometimes the neurological manifestations can precede the typical features like fever and cough and later on typical manifestations develop in these patients. Hence a high index of suspicion is required for timely diagnosis and isolation of cases to prevent the spread in neurology wards. We present a narrative review of the neurological manifestations and complications of COVID-19. Our aim is to update the neurologists and physicians working with suspected cases of COVID-19 about the possible neurological presentations and the probable neurological complications resulting from this novel virus infection.

Neuro-rehabilitation services are essential in reducing post-stroke impairments, enhancing independence, and improving recovery in hospital and post-discharge. However these services are therapist-dependent and resource intensive. Patients’ disengagement and boredom in stroke units are common which adversely affect functional and psychological outcomes. Novel techniques such as use of iPads™ are increasingly researched to overcome such challenges. The aim of this review is to determine the feasibility, effectiveness, acceptability, and barriers to the use of iPads™ in stroke neuro-rehabilitation. Four databases and manual literature search were used to identify published studies using the terms “iPad”, “Stroke”, and “neuro-rehabilitation”. Studies were included in accordance with the review selection criteria. A total of 16 articles were included in the review. The majority of the studies focused on iPads use in speech and language therapy. Although of small scale, the studies highlighted that iPads are feasible, have the potential to improve rehabilitation outcomes, and can improve patient’s social isolation. Patients’ stroke severity and financial limitations are some of the barriers highlighted in this review. This review presents preliminary data supportive for the use of iPad technology in stroke neuro-rehabilitation. However, further research is needed to determine impact on rehabilitation goals acquisition, clinical efficacy, and cost-efficiency.

Background: Previously, our laboratory has provided evidence that pre-administration of the antioxidant, lipoic acid covalently bonded to various naturally occurring antioxidants, enhanced neuroprotective capacity compared to the administration of lipoic acid on its own. The naturally occurring compound scopoletin, a coumarin derivative, has been shown in various in vitro studies to have both antioxidant and anti-inflammatory mechanism of actions. To date, the effect of scopoletin on neuronal cell death in an in vivo model of ischemia or ischemia-reperfusion has not been investigated. Therefore, the present investigation was designed to determine if scopoletin on its own, or a co-drug consisting of lipoic acid and scopoletin covalent bond, named UPEI-400, would be capable of demonstrating a similar neuroprotective efficacy. Methods: Using a rodent model of stroke in male rats (anesthetized with Inactin®; 100 mg/kg, iv), the middle cerebral artery was permanently occluded for 6 hours (pMCAO), or in separate animals, occluded for 30 min followed by 5.5 hrs of reperfusion (ischemia/reperfusion; I/R). Results: Pre-administration of either scopoletin or UPEI-400 significantly decreased infarct volume in the I/R model (p<0.05), but not in the pMCAO model of stroke. However, UPEI-400 was ~1000 times more potent as compared to scopoletin on its own. The optimal dose of UPEI-400 was then injected during the occlusion and at several time points during reperfusion and significant neuroprotection was observed for up to 150 mins following the start of reperfusion (p<0.05). Conclusion: The data suggest that synthetic combination of scopoletin with lipoic acid (UPEI-400) is a more effective neuroprotectant that either compound on their own. Also, since UPEI-400 was only effective in a model of I/R, it is possible that it may act to enhance neuronal antioxidant capacity and/or upregulate anti-inflammatory pathways to prevent the neuronal cell death.

Muscle mass at admission is important to survive stroke, and stroke-induced sarcopenia is a serious problem because of its poor prognosis. Muscle mass measurement and monitoring are essential for appropriate re-habilitation and nutrition management. Several methods are used to assess skeletal muscle mass in stroke, such as computed tomography (CT), ultrasonography, bioelectrical impedance analysis, dual-energy X-ray absorptiometry, biomarkers, and anthropometrics. In stroke, a head CT is used to estimate muscle mass by measuring the temporal muscle. However, it is mostly retrospectively conducted due to radiation exposure. After stroke, limb muscle atrophy and diaphragm dysfunction are observed using ultrasound. However, ultrasound requires an understanding of the methods and skill. A bioelectrical impedance analysis can be used to assess muscle mass in patients after a stroke unless they have dynamic fluid changes. Dual-energy X-ray absorptiometry is used for follow-up after hospital discharge. Urinary titin N-fragment and serum C-terminal agrin fragment reflect muscle atrophy after stroke. Anthropometrics may be useful with limited resources. We summarized the features of each measurement and proved the recent evidence to properly measure and monitor skeletal muscle mass after stroke.

Introduction: Epilepsy is one of the most common neurological diseases. Epilepsy poses a significant burden on the quality of life of affected individuals and their families. The aim of this study was to determine the psychiatric disorders in epileptic patients. Methods and Materials: This descriptive-analytical study was conducted in 2017 with a simple random sampling method on patients with epilepsy who admitted to the neurology department. Results: Among the 150 examined patients, 88 (58.7%) were female and 63(42%) had epilepsy more than 10 years. The most common psychiatric disorder among epileptic patients was depression (68 patients = 45.3%) and anxiety (65 patients = 43.3%) patients. Conclusion: Most of patients had more than 10 years history of epilepsy. Also, Anxiety and depression were the most common symptoms in epileptic patients. It need to more study to determine the psychiatric disorders in epileptic patients.

The aim of this research was to investigate the mass, substances and energy flow through two-stroke low speed Diesel engines. For this reason, a zero-dimensional model of the combustion in the engine was developed with a calculated amount and composition of exhaust gases. Due to the large amount of oxygen in the exhaust gases, a ratio of real air consumption and stoichiometric amount of air required for combustion of injected fuel was set. The calculated ratio showed that the engine consumes four times more air than needed for combustion in AFR_stoich. In this work it is called the Air Consumption Factor or Ratio and has not been mentioned in scientific literature before. Air Consumption Ratio is defined as a factor of dry or humid air. To be more comprehensive, a modified diagram of composition of the flow in and out of a two-stroke fuel injection engine and the cylinder was drawn.

During middle age, women are less susceptible to nonalcoholic steatohepatitis (NASH) than men. Thus, we investigated the underlying molecular mechanisms behind these sexual differences using an established rat model of NASH. Mature female and male stroke-prone spontaneously hypertensive 5/Dmcr rats were fed control or high-fat-cholesterol (HFC) diets for 2, 8, and 14 weeks. Although HFC-induced hepatic fibrosis was markedly less severe in females than in males, only minor gender differences were observed in expression levels of cytochrome P450 enzymes (CYP)7A1, CYP8B1 CYP27A1, and CYP7B1, and multidrug resistance-associated protein 3, and bile salt export pump, which are involved in fibrosis-related bile acid (BA) kinetics. However, the BA detoxification-related enzymes UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) 2A1, and the nuclear receptors constitutive androstene receptor (CAR) and pregnane X receptor (PXR), were strongly suppressed in HFC fed males, and were only slightly changed in HFC-diet fed females. Expression levels of the farnesoid X receptor and its small heterodimer partner were similarly regulated in a gender-dependent fashion following HFC feeding. Hence, the pronounced female resistance to HFC-induced liver damage likely reflects sustained expression of the nuclear receptors CAR and PXR and the BA detoxification enzymes UGT and SULT.

Populations with essential hypertension have a high risk of nonalcoholic steatohepatitis (NASH). In this study, we investigated the mechanism that underlies the progression of hypertension-associated NASH by comparing differences in the development of high fat and cholesterol (HFC) diet-induced NASH among three strains of rats, i.e., two hypertensive strains comprising spontaneously hypertensive rats and the stroke-prone spontaneously hypertensive 5/Dmcr, and the original Wistar Kyoto rats as the normotensive control. We investigated histopathological changes and molecular signals related to inflammation in the liver after feeding with the HFC diet for 8 weeks. The diet induced severe lobular inflammation and fibrosis in the livers of the hypertensive rats, whereas it only caused mild steatohepatitis in the normotensive rats. Increased activation of proinflammatory signaling (transforming growth factor-β1/mitogen-activated protein kinases pathway) was observed in the hypertensive strains fed with the HFC diet. In addition, the HFC diet suppressed the nuclear factor erythroid 2-related factor 2 pathway in the hypertensive rats and led to lower increases in the hepatic expression of heme oxygenase-1, which has anti-oxidative and anti-inflammatory activities. In conclusion, these signaling pathways might play crucial roles in the development of hypertension-associated NASH.

Acute ischemic strokes are the third leading cause of death and the leading cause of neurological disability worldwide. The oxygen and glucose deprivation associated with ischemic strokes not only leads to neuronal cell death, but also increases the inflammatory response and decreases functional output of the brain. The only intervention approved by US Federal Drug and Food Administration for treatment of ischemic strokes is tissue plasminogen activator (tPA), however, such treatment can only be given within 4.5 hours of the onset of stroke-like symptoms. This narrow time-range limits its application, and it also might induce detrimental rather than beneficial effects to stroke patients by treatment of the tPA. In order to reduce the infarct volume of an acute ischemic stroke while increasing the time period for treatment, emerging therapies reveal great potential by targeting inflammation, growth factors, ion channels, and neurotransmitter receptors with monoclonal antibody (MAB). With successfully application in the treatment of cancer patient by MAB, in this review, we will focus on recent advances on stroke therapy by using MAB on the treatment of stroke by targeting inflammation, growth factors, ion channels, and neurotransmitter receptors. Therefore, developing specific MAB targeting the signaling pathway of stroke will contribute to stroke therapy.

Beyond their significant contribution to the dietary and industrial supplies, marine algae are considered to be a potential source of some unique metabolites with diverse health benefits. The pharmacological properties, such as antioxidant, anti-inflammatory, cholesterol homeostasis, protein clearance and anti-amyloidogenic potentials of algal metabolites endorse their protective efficacy against oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired proteostasis which are known to be implicated in the pathophysiology of neurodegenerative disorders and the associated complications after cerebral ischemia and brain injuries. As was evident in various preclinical studies, algal compounds conferred neuroprotection against a wide range of neurotoxic stressors, such as oxygen/glucose deprivation, hydrogen peroxide, glutamate, amyloid β, or 1-methyl-4-phenylpyridinium (MPP+) and, therefore, hold therapeutic promise for brain disorders. While a significant number of algal compounds with promising neuroprotective capacity have been identified over the last decades, a few of them have had access to clinical trials. However, the recent approval of an algal oligosaccharide, sodium oligomannate, for the treatment of Alzheimer's disease enlightened the future of marine algae-based drug discovery. In this review, we briefly outline the pathophysiology of neurodegenerative diseases and brain injuries for identifying the targets of pharmacological intervention, and then review the literature on the neuroprotective potentials of algal compounds along with the underlying pharmacological mechanism, and present an appraisal on the recent therapeutic advances. We also propose a rational strategy to facilitate algal metabolites-based drug development.

Abstract: 1) Background: The present study aimed to examine the effect of the instructional intervention in family caregivers’ perceived threat of stroke patients’ dependency risk. 2) Methods: This was a randomized controlled clinical trial in which two patient and family caregiver groups of 45 were randomly divided into intervention and control groups based on the inclusion/exclusion criteria. Instructional intervention for family caregivers in the intervention group was in the form of four one-hour sessions. The data were collected before and immediately after instructional intervention at the hospital as well as two weeks and two months following the intervention via postal service. The data analysis was done using SPSS ver.22. 3) Results: The pre-intervention family caregivers’ perceived threat was not significantly different in the two groups (P = 0.591). However, the family caregivers’ perceived threat of the intervention group increased after the intervention compared with the control group (P < 0.001). In addition, the family caregivers’ perceived threat of the intervention group was significantly different in all post instructional intervention stages compared with pre-intervention (P < 0.001), whereas no such difference was observed in the control group (p = 0.245). 4) Conclusions: It is recommended that stroke patients' caregivers be provided with instructional programs to enhance their understanding of patient dependency risks and challenges.

Background: Nearly two-thirds of acute stroke patients have dysphagia. Dysphagia is difficulty to swallow food or liquids. Early detection of dysphagia is crucial in stroke patients as a result of increased morbidity and mortality due to malnutrition and respiratory tract infections. Aim: Our purpose was to conduct a literature review of dysphagia screening for stroke patient. Methods: We used the bolean operator to search articles of “or” and “and” with the key words were "Dysphagia" or “Screening”, AND "Stroke" or Acute Stroke” AND "Nursing". Data based used were Scopus, Proquest and Science Direct with inclusion criteria using full text in English which published from 2019 to 2021. We obtained 240 articles and then we screened by reading the main focus of articles with paying attention to the topics and the suitability of article content.Result: Twenty five publications relating to dysphagia screening met the inclusion criteria. There are five methods of dysphagia screening performed by nurses or other health workers: 1) a simple Questionnaire Test (4QT) method; 2) Water Swallow Test (WST) method; 3) Bed Side Screening Tool for Dysphagia (BSTD) method; 4) Volume Viscosity Swallow Test (V-VST) method; 5) EAT-10 method.Conclusion: screening is the first step in the identification of swallowing impairment or dysphagia of stroke patient. Dysphagia is an independent predictor of poor patient outcome and prolonged recovery time. Nurse has an important role to conduct a screening and must ensure that the selected tools has high reliability and concurrent validity. Key Words: Dysphagia, Nursing, Screening, Stroke

In advanced world stroke is one of the disabling cause of death that can be managed with thrombolysis if presents early despite further risk of intracerebral haemorrhage. Secondary prevention is an important objective in ischaemic stroke where recurrence is very high with subsequent stroke. Carotid End Arterectomy impact a definitive and effective role for both symptomatic and asymptomatic carotid stenosis for secondary stroke prevention in selective cases. Thrombolysis is a potential primary management for certain group whereas carotid surgery employs secondary preventative measure in a specified ischaemic stroke group.

Objective: It was aimed to investigate the cerebral vascular territories in stroke patients with NVAF as an etiologic factor. Material and Methods: A total of 104 patients who were referred to our hospital between January 2015 and September 2016, who were over 55 years of age, identified or documented as having a standard ECG or Holter ECG record on their medical history, and diagnosed with stroke were included. Our study was designed as a retrospective analysis of prospective data. Detailed history, physical examination and electrocardiography (ECG) evaluations of the patients were performed. Descriptive statistics were used in the detection of findings, and t-test, Pearson-square test and Fisher's exact test were used for differences analysis. Results: 53.8% (N = 56) of the patients were male and 46.2% (N = 48) were female. The mean age was 73.5. MCA was the most common site of vascular involvement in NVAF-dependent strokes. In MCA vascular territory, ischemic infarcts were detected most frequently in the upper and lower divisions. SCA and PCA followed MCA. Approximately 64% of the NVAF-related strokes were anterior circulation infarction (ASE) and 22% were posterior circulation infarct (PSE). There was a significant difference in age and past stroke history factors in favor of ASE (p<0.05). There was no significant difference between ASE and PSE in HT, cardiac history and DM factors (p>0.05). Conclusion: It was emphasized that the area of the vessel that underwent ischemia in the acutely displayed infarcts and the etiological factor for this vessel area could be predicted

The neurovascular niche is crucial for constant blood supply and blood-brain barrier (BBB) function and is altered in a number of different neurological conditions, making this an intensely active field of research. Brain vasculature is unique for its tight association of endothelial cells with astrocytic endfeet processes. Separation of the vascular compartment by centrifugation-based methods confirmed enrichment of astrocytic endfeet processes, making it possible to study the entire vascular niche with such methods. Several centrifugation-based separation protocols are found in the literature; however, with some constraints which limit their applicability and the scope of the studies. Here, we describe and validate a protocol for physically separating the neurovascular niche from the parenchyma, which is optimized for smaller tissue quantities. Using endothelial, neuronal and astrocyte markers, we show that quantitative Western blot-based target detection can be performed of both the vascular and parenchymal fractions using as little as a single mouse brain hemisphere. Validation of our protocol in rodent stroke models by detecting changes in serum albumin signals and astrocyte activation, i.e. increased glial fibrillary acidic protein expression, between the ipsilateral and the lesion-free contralateral hemisphere demonstrates this protocol as a new way of detecting BBB breakdown and astrogliosis, respectively.

Aphasia is one of the most socially disabling post-stroke deficits. Although traditional therapies have been shown to induce adequate clinical improvement, aphasic symptoms often persist. Therefore, new rehabilitation techniques which act as a substitute or as an adjunct to traditional approaches are urgently needed. The present review provides an overview of the efficacy and safety of the most innovative approaches which have been proposed over the last twenty years. First, we examined the effectiveness of the pharmacological approach, principally used as an adjunct to language therapy, reporting the mechanism of action of each single drug for the recovery of aphasia. Results are conflicting but promising. Secondly, we discussed the application of Virtual Reality (VR) which has been proved to be useful since it potentiates the ecological validity of the language therapy by using virtual contexts which simulate real-life everyday contexts. Finally, we focused on the use of Transcranial Direct Current Stimulation (tDCS), both discussing its applications at the cortical level and highlighting a new perspective, which considers the possibility to extend the use of tDCS over the motor regions. Although the review revels an extraordinary variability among the different studies, substantial agreement has been reached on some general principles, such as the necessity to consider tDCS only as an adjunct to traditional language therapy.

Controlling Nutritional Status (CONUT) Score is useful for the nutritional screening. We aimed to explore whether the CONUT score may predict a 3-month functional outcome in hemorrhagic stroke (AHS). Totally, 349 patients with incident AHS were consecutively recruited, and their malnutrition risks were determined using a high CONUT score of ≥ 2. Poor functional outcomes were defined as the modified Rankin Scale (mRS) score of ≥ 3 at 3 months. A total of 328 patients (mean age, 60.4 ± 12.83 years; 66.8% male) were included, 172 (52.40%) patients at malnutrition risk and 104 (31.7%) patients with a poor prognosis. High-CONUT patients had lower total lymphocyte counts and total cholesterol levels than low-CONUT patients (p &lt; 0.001 and p = 0.012). At 3-month post discharge, patients with malnutrition risk had higher hospitalization costs (p = 0.021), lower Barthel Index (p = 0.001), and more infectious complications (p = 0.002) than those without, and there was a greater risk for poor functional outcomes in the high-CONUT compared with the low-CONUT patients at admission (adjusted odds ratio: 2.32, 95% confidence interval: 1.28-4.17). High-CONUT scores predict a 3-month poor prognosis in AHS, which may help identify the AHS patients who need additional nutritional managements.

(1) Background: Existing research has demonstrated the potential of mHealth apps in improving the caregiving outcomes of stroke. Since several apps were published in commercially available app stores without explaining their design and evaluation processes, it is necessary to identify the usability and user experience issues to promote long-term adherence and usage; (2) Methods: User reviews were extracted from the 47 previously identified apps that support stroke caregiving needs using a python-scraper. The reviews were pre-processed and filtered using python scripts. The final corpus was classified based on usability and user experience dimensions to highlight issues within the app; (3) Results: A total of 162,095 were extracted from the two app stores. After filtration, 15,818 reviews were included and classified based on the usability and user experience dimensions. Findings highlight critical issues related to the errors/effectiveness, efficiency and support that contribute to decreased satisfaction, emotion and frustration in using the app; (4) Conclusion: The study identified several usability and user experience issues due to the inability of the app developers to understand the needs of the user. Further, the study describes the inclusion of a participatory design approach to promote an improved understanding of user needs; therefore, limiting any issues and ensuring continued use.

This study used structural equation modelling (SEM) to evaluate the direct effect of sex and age on stroke types and outcomes in Tertiary Health Facilities in Rives State, Nigeria. The study was a cross-sectional retrospective hospital-based research that utilized specific stroke patients’ information between 2015-2019. The study obtained the sex and age, stroke type (ischemic/hemorrhagic), and outcomes (No disability/disability/death) from the records. The retrieved data was Microsoft Excel (2016), then analyzed using SPSS (version 21, Amos) and STATGRAPHICS centurion (Stat Point Tech., Inc.). From the result, out of the recorded 1916 stroke patients, 1229 (64.1%) were female, while 687 (35.9%) were males. The older adults (>55 years) had more recorded cases (n=1289) than young adults (ages 18–35 years; n=77) and middle-aged adults (ages 36–55 years, n=550). The SEM results showed that age was significantly associated with stroke type (P<0.001) and outcomes (P=0.038), while sex was significantly associated with stroke outcomes (P<0.001). The likelihood of death was 1.3 times higher in hemorrhagic stroke than ischemic stroke. In conclusion, age and sex had direct effects on stroke type, while age had a direct effect on stroke outcome. Hemorrhagic stroke was more likely to cause death than ischemic stroke in the studied population.

Ischemic Stroke precedes depression . Post Stroke Depression (PSD) is a major driver for poor recovery, negative quality of life, poor rehabilitation outcomes and poor functional ability. This systematic reviews confirmed the post stroke depression as the norm as complex ischemic cascade involve the bioenergetic failure, deranged iron homeostasis ( calcium influx, Na influx, potassium efflux etc) excitotoxicity, acidotoxicity,disruption of the blood brain barrier, cytokine mediated cytotoxicity, reactive oxygen mediated toxicity , activation of cyclooxygenase pathway and generation of toxic products, infiltration of immune mediated cells resulting the cell death and deranged neuronal networks in mood related brain regions. This review focus on the pathobiology of stroke in the context and make the argument that PSD is the norm after a stroke rather than the exception.

Background. Specific clinical risk factors that may be associated with ambulatory outcome following thrombolysis therapy in ischemic stroke patients with pre-stroke depression is not fully understood. This was investigated. Methods. Multivariate analyses were performed to identify predictors of functional ambulatory outcomes. Patient demographics and clinical risk factors served as predictive variables, while improvement or no improvement in ambulatory outcome was considered as the primary outcome. Results. A total of 595 of these patients received rtPA of which 310 patients presented with pre-stroke depression, 217 had no improvement in functional outcome, while 93 patients presented with an improvement in functional outcome. Carotid artery stenosis (OR= 11.577, 95% CI, 1.281 – 104.636, P=0.029) and peripheral vascular disease (OR= 18.040, 95% CI, 2.956-110.086, P=0.002) were more likely to be associated with an improvement in ambulation. Antihypertensive medications (OR= 7.810, 95% CI, 1.401 –43.529, P=0.019),previous TIA (OR= 0.444, 95% CI, 0.517 –0.971, P=0.012), and congestive heart failure (OR= 0.217, 95% CI, 0.318 –0.402, P=0.030) were associated with a no improvement in ambulation. Conclusion. After adjustment for covariates, more clinical risk factors were associated with no improvement when compared with improvement in functional outcome following thrombolysis therapy in an acute ischemic stroke population with pre-stroke depression.

The Japanese Association for Acute Medicine Committee recently proposed a novel classification system for the severity of heat-related illnesses. The illnesses are simply classified into three stages based on symptoms and management or treatment. Stages I, II, and III broadly correspond to heat cramp and syncope, heat exhaustion, and heat stroke, respectively. Our objective was to examine whether this novel severity classification is useful in the diagnosis by healthcare professionals of patients with severe heat-related illness and organ failure. A nationwide surveillance study of heat-related illnesses was conducted between June 1 and September 30, 2012, at emergency departments in Japan. Among the 2130 patients who attended 102 emergency departments, the severity of their heat-related illness was recorded for 1799 patients, who were included in this study. In the patients with heat cramp and syncope or heat exhaustion (but not heat stroke), the blood test data (alanine aminotransferase, creatinine, blood urea nitrogen, and platelet counts) for those classified as stage III were significantly higher than those of patients classified as stage I or II. There were no deaths among the patients classified as stage I. This novel classification may avoid underestimating the severity of heat-related illness.

The global burden of stroke is still high, particularly in developing countries, with hypertension serves as the main risk factor. Knowledge related to stroke is essential to establish better prevention strategies. This study aimed to identify factors associated with stroke awareness among hypertensive patients in Indonesia. This was a cross-sectional study conducted in five Community Health Centers in Indonesia. We used a standardized questionnaire to asses stroke awareness and the influencing factors. The knowledge on hypertension was assessed using Hypertension Knowledge Level Scale (HK-LS). Multivariate logistic regression analysis was performed to measure factors associated with stroke awareness. A total of 457 hypertensive patients were included. Majority of patients (77.46%) had low stroke awareness. Having higher knowledge on hypertension, higher income, and a history of previous stroke were associated with higher level of stroke awareness (odds ratio [OR] 1.878, 95%CI 1.176-2.999, p 0.008; OR 1.887, 95%CI 1.170-3.045, p 0.009; OR 5.276, 95%CI 2.210-12.594, p<0.001, respectively). This study suggests that knowledge on hypertension, income, and history of previous stroke are factors which may influence the level of stroke awareness. This emphasizes the need to provide better campaign and education program to raise stroke awareness in a community setting.

Background: Antiplatelet medications such as aspirin and clopidogrel are used following thrombotic stroke or transient ischemic attack (TIA) to prevent a recurrent stroke. However, the antiplatelet treatments fail frequently, and patients experience recurrent stroke. One approach to lower the rates of recurrence, may be the individualized antiplatelet therapies (antiplatelet therapy modification (ATM)) based on the results of platelet function analysis (PFA). This review was undertaken to gather and analyse the evidence about the effectiveness of such approaches. Methods: We searched Medline, CINAHL, Embase, Web of Science and Cochrane databases to 7 January 2020. Results: Two observational studies involving 1136 patients were included. The overall effects of PFA-based ATM on recurrent strokes (OR 1.05; 95% CI 0.69 to 1.58), any bleeding risk (OR 1.39; 95% CI 0.92 to 2.10) or death hazard from any cause (OR 1.19; 95% CI 0.62 to 2.29) were not significantly different from the standard antiplatelet therapy without ATM. Conclusions: The two studies showed opposite effects of PFA-guided ATM on the recurrent strokes in aspirin non-responders, leading to an insignificant difference in the subgroup meta-analysis (OR 1.59; 95% CI 0.07 to 33.77), while the rates of any bleeding events (OR 1.04; 95% CI 0.49 to 2.17) or death from any cause (OR 1.17; 95% CI 0.41 to 3.35) were not significantly different between aspirin non-responders with ATM and those without ATM. There is a need for large randomized controlled trials which account for potential confounders such as ischemic stroke subtypes, technical variations in the testing protocols, patient adherence to therapy, and pharmacogenetic differences.

We aimed to reveal the disease burden of aphasia after acute ischemic stroke (AIS) at the national level and investigate the impact of aphasia on tertiary care resources and patient outcomes. The local database from the Cluj-Napoca Emergency County Hospital (CNECH), the second largest stroke center in Romania was used to export demographics, baseline clinical and laboratory data, inpatient length of stay (LOS), NIH Stroke Scale (NIHSS), and discharge modified Rankin Scale (mRS) score data for all AIS patients admitted during March 2019. Of 92 patients included in the study, 30 (32.6 %) had aphasia on admission. In a marginally significant unadjusted hierarchical multiple regression model, individuals with aphasia had a LOS of 1.86 days longer than stroke survivors without aphasia. In an adjusted version of the model, the NIHSS score at baseline was a significant predictor for LOS. In addition, the presence of aphasia was associated with a 1.49 increase in the mean mRS score. Aphasia was a marginally significant predictor for increased LOS. Presence of aphasia was more likely to produce a poor functional outcome. Considering an estimated impact of approximately EUR 3 million on direct medical expenditure annually, future policymaking efforts should improve prevention of stroke and improved access to post-stroke aphasia care in Romania.

Early stroke diagnosis remains a big challenge in healthcare partly due to the lack of reliable diagnostic blood biomarkers, which in turn leads to increased rates of mortality and disability. Current screening methods are optimised to identify patients with a high risk of cardio-vascular disease, especially among the elderly. However, in young adults and children, these methods suffer low sensitivity and specificity and contribute to further delays in their triage and diagnosis. Accordingly, there is an urgent need to develop reliable blood biomarkers for triaging patients suspected of stroke in all age groups, especially children and young adults. This review explores some of the existing blood biomarkers, as single biomarkers, or biomarker panels, and examine their sensitivity and specificity for predicting stroke. A review was performed on PubMed and Web of Science for journal articles published in English during the period 2001 to 2021 which contained information regarding biomarkers of stroke. In this review article, we provide comparative information on the availability, clinical usefulness, and time-window periods of eight single blood biomarkers and six biomarker panels that have been used for predicting stroke in emergency situations. The outcomes of this review can be used in future research for developing more effective stroke biomarkers.

It is widely known that vitamin D receptors have been found in neurons and glial cells and their highest expression is in the hippocampus, hypothalamus, thalamus and subcortical grey nuclei, and substantia nigra. The vitamin D helps the regulation of neurotrophin, neural differentiation and maturation, through the control operation of growing factors synthesis (ie NGF and GDNF), the trafficking of the septo-hyppocampal pathway, and the control of the synthesis process of different neuromodulators (such as Ach, DA, and GABA). Based on these assumptions, we have written this review in order to summarize the potential role of vitamin D in neurological pathologies. The work could be titanic, and might result very fuzzy and even incoherent, if we would not have conjectured to taper our first intentions and devoted our interests towards three mainstreams: demyelinating pathologies, vascular syndromes and neurodegeneration. Due to the lack of effective therapeutic options, a part from the disease modifying strategies, the role of different risk factors should be investigated in neurology, as far as their correction may lead to the improvement of the cerebral conditions. We have explored the relationships between the gene-environmental influence and long term vitamin D deficiency, as a risk factor for the development of different types of neurological disorders, along with the role and the rationale of therapeutic trials with vitamin D implementation.

Medical brain image analysis is a necessary step in the Computers Assisted /Aided Diagnosis (CAD) systems. Advancements in both hardware and software in the past few years have led to improved segmentation and classification of various diseases. In the present work, we review the published literature on systems and algorithms that allow for classification, identification, and detection of White Matter Hyperintensities (WMHs) of brain MRI images specifically in cases of ischemic stroke and demyelinating diseases. For the selection criteria, we used the bibliometric networks. Out of a total of 140 documents we selected 38 articles that deal with the main objectives of this study. Based on the analysis and discussion of the revised documents, there is constant growth in the research and proposal of new models of deep learning to achieve the highest accuracy and reliability of the segmentation of ischemic and demyelinating lesions. Models with indicators (Dice Score, DSC: 0.99) were found, however with little practical application due to the uses of small datasets and lack of reproducibility. Therefore, the main conclusion is to establish multidisciplinary research groups to overcome the gap between CAD developments and their complete utilization in the clinical environment.

Stroke is one of the most prevalent cardiovascular diseases worldwide, both in high-income countries and in medium and low-medium income countries. The WHO report on non-communicable diseases (NCDs) indicates that the highest behavioral risk in NCDs is attributable to incorrect nutrition. The objective of our work is to present an overview of meta-analyses that have investigated the impact of different foods and / or drinks in relationship with the risk of stroke events (ischemic/ hemorrhagic). The papers to be included in the overview were sought in the MEDLINE, EMBASE, Scopus, Clinicaltrials.gov, Web of Science, and Cochrane Library and were selected according to PRIMA flow chart. Quality assessment were made according to AMSTAR scale. This overview shows that all primary studies came from countries with high income level. This evidence shows that many countries are not represented. Therefore, different lifestyles, ethnic groups, potentially harmful or virtuous eating habits are not reported. It is important to underline how the choose of foods may help reduce the risk of cardiovascular diseases and stroke in particular.

Background: Many randomized controlled trials (RCTs) and systematic reviews (SRs) on acupuncture treatment for post-acute stroke dysphagia have been published. Due to conflicting results an overview of SRs to summarize and assess the quality of this evidence to determine whether acupuncture is effective for this disease was conducted. Methods: Seven databases were searched for SRs and/or Meta-analysis of RCTs and quasi-RCTs on acupuncture for post-acute stroke dysphagia. Two authors independently identified SRs and meta-analyses, collected data to assess the quality of included SRs and meta analyses according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the revised Assessment of Multiple Systematic Reviews (AMSTAR 2). Results: 31 SRs were identified. Quality of 22 SRs was critically low, 5 SRs were low, and 4 Cochrane SRs were moderate when evaluated by AMSTAR2. 17 SRs reported 85.2-96.3% items of PRISMA. Five SRs included explanatory RCTs, 16 SRs included pragmatic RCTs, and 10 SRs included both. Conclusion: Currently evidence on the effectiveness of acupuncture on post-acute stroke dysphagia is low quality. Type of study appeared to have no direct influence on the result, but the primary outcome measures showed a relationship with the quality of SRs. High quality trials with large sample sizes should be the focus of future research. PROSPERO REGISTRATION NUMBER: CRD42019134163

Background: This study investigated the prevalence of worsening problems using Post Stroke Checklist (PSC) at 3, 6, and 12 months post-stroke and their associations with health-related quality of life. Methods: In stroke patients admitted between June 2014 and December 2015, PSC and EuroQol-5Dthree level (EQ-5D-3L) were assessed at post-stroke 3 (n=181), 6 (n=175), and 12months (n=89). The prevalence of worsening problems and its association withEQ-5D-3L at post-stroke 3 and 6months were analyzed. Results: An average of 0.59 (range 0–12), 1.47 (range 0–12), and 1.00 (range 0–10) worsening problems per patient was identified at 3, 6, and 12months after stroke, respectively. The most frequently and continuously identified worsening problems were mood disturbances (reported by 8.8%, 16.0% and13.5% of patients at 3, 6, and 12 months post-stroke, respectively). Worsening mobility was significantly associated with worse EQ-5D index at post-stroke 3 months (β,-0.583; 95% CI, -1.045 to -0.120). The worsening of mobility and communication was significantly associated with worse EQ-5D index at post-stroke 6 months (mobility: β,-0.170; 95% CI, -0.305 to -0.034, communication: β,-0.164; 95% CI, -0.309 to -0.020). Conclusions: PSC may be useful for the detection of various subjective worsening problems during serial clinical follow-up after stroke. Appropriate rehabilitation and management strategy to solve the identified problems could improve the quality of life in stroke survivors.

General characteristics of K changes together with their fine structure associated with ground flashes in Sri Lanka in the tropics are presented. It is found that on average there are about 2 K changes associated with each return stroke. Analysis of the fine structure of the K changes shows that the K change is a chaotic pulse burst. Some of these chaotic pulse bursts start and the others end as a regular pulse bursts. Sometimes the chaotic part occurs in between two regular pulse bursts. This is in agreement with the recent published results that claim that chaotic pulse bursts are a random superposition of regular pulse bursts. The results show that the small step fields identified in the literature as K changes are the static fields associated with these pulse bursts.

Stroke is one of the leading cause of adult disability and the second leading cause of death worldwide. The immune system actively participates in the pathobiological process of AIS, during the index event and during the repair process despite the limited attention drawn to this aspect in the existing stroke guidelines globally. The similar clinical course and similar circulating innate and adaptive immune cell counts in AIS and COVID-19 has created a renewed interest in these easily available biomarkers innate and adaptive immunological changes in AIS with potential diagnostic, prognostic, and therapeutic implications. The current scoping review aimed to assess the significance of circulating neutrophil and lymphocyte counts and their ratio (NLR) in AIS and explore their association with post-stroke recovery trajectory. The Arksey and O'Malley methodological framework was employed to review the published papers on the neutrophil-lymphocyte ratio (NLR) and AIS in late November 2020. Only studies published in English from 2000-2020 were included in this scoping review. Fifty-three published papers were reviewed. This review's key finding is that a canonical inflammatory response occurs in AIS just as in the case of COVID-19 and neurological involvements well described in the recent literature. An excessive circulating innate immune cells (neutrophils) and reduced circulating adaptive immune cells (lymphocytes ) are associated with poorer outcomes during the acute interventions ( reperfusion therapies) as well as the recovery trajectory. Main representatives of innate and adaptive immunity follow a canonical course in AIS and COVID-19. Exaggerated circulating innate ( elevated neutrophils and elevated NLR) and reduced adaptive immune response (lymphopenia) correlate with the worse outcome in AIS and COVID-19. This scoping review's findings make the strongest case for a systems biology-based approach to the standard operating procedures in stroke care urgently.

Ischemia stroke is one of a clinically common cerebrovascular disease. And Inhibition of brain tissue ischemia and reperfusion-induced damage, especially apoptosis, has an irreplaceable protective effect on ischemic nerves, and has special significance for the treatment of patients after treatment. However, the development of neuroprotective drugs still has certain challenges. Radix scrophulariae as a valuable medicine, has been discovered to has neuroprotective effects. Our researches initially proved that Radix scrophulariae aqueous extract (RSAE) exerting a neuroprotective effects on cerebral ischemia and reperfusion (I/R) injury in oxygen glucose deprivation and reperfusion (OGD/R)-induced PC12 cells and middle cerebral artery occlusion/reperfusion (MCAO/R) model mice, were associated with attenuation of infarct volume, brain water content, nitric oxide (NO) and malondialdehyde (MDA), inhibiting I/R-induced damage by reducing the levels of LDH release, improving anti-oxidant capacity by upregulating the SOD, GSH-Px and CAT activity, stabilizing mitochondrial membrane potential, reducing neuronal apoptosis, necrosis and neuronal loss by regulating the expression of anti-apoptotic BCL-2and pro-apoptotic protein Bax, and elucidating downregulate the phosphorylation levels of MAPK pathways. Our findings may elaborate the neuroprotective effects and potential mechanisms of RSAE on focal cerebral I/R injury in mice. Since, Radix scrophulariae, as a potential neuroprotective natural plant, has originally been identified to, our results may offer directions and clues for discovering new active compounds or drugs for treatment of ischemic stroke, which allows us to discover many new natural active chemicals by chemical separation and identification, and provide new insights into therapeutic targets in stroke patients.

Objectives: Studies evaluating machine learning (ML) algorithms on cross-lingual RadLex® mappings for developing context-sensitive radiological reporting tools are lacking. Therefore, we investigated whether ML-based approaches can be utilized to assist radiologists in providing key imaging biomarkers – such as The Alberta stroke programme early CT score (APECTS). Material and Methods: A stratified random sample (age, gender, year) of CT reports (n=206) with suspected ischemic stroke was generated out of 3997 reports signed off between 2015-2019. Three independent, blinded readers assessed these reports and manually annotated clinico-radiologically relevant key features. The primary outcome was whether ASPECTS should have been provided (yes/no: 154/52). For all reports, both the findings and impressions underwent cross-lingual (German to English) RadLex®-mappings using natural language processing. Well-established ML-algorithms including classification trees, random forests, elastic net, support vector machines (SVMs) and boosted trees were evaluated in a 5 x 5-fold nested cross-validation framework. Further, a linear classifier (fastText) was directly fitted on the German reports. Ensemble learning was used to provide robust importance rankings of these ML-algorithms. Performance was evaluated using derivates of the confusion matrix and metrics of calibration including AUC, brier score and log loss as well as visually by calibration plots. Results: On this imbalanced classification task SVMs showed the highest accuracies both on human-extracted- (87%) and fully automated RadLex® features (findings: 82.5%; impressions: 85.4%). FastText without pre-trained language model showed the highest accuracy (89.3%) and AUC (92%) on the impressions. Ensemble learner revealed that boosted trees, fastText and SVMs are the most important ML-classifiers. Boosted trees fitted on the findings showed the best overall calibration curve. Conclusions: Contextual ML-based assistance suggesting ASPECTS while reporting neuroradiological emergencies is feasible, even if ML-models are restricted to be developed on limited and highly imbalanced data sets.

An early hypothesis in robot-assisted stroke therapy was that sensorimotor stimulation through robotic assistance is beneficial for recovery. Despite 25 years of upper-limb rehabilitation robotics research, this hypothesis remains untested barring a few studies with small sample sizes. This review aims to provide a critical summary of the current state of this hypothesis by collating evidence from rehabilitation robotics and other related therapeutic approaches. The review starts with a causal model to expose the various direct and indirect routes through which robotic assistance can aid sensorimotor recovery. The indirect routes include the influence of robotic assistance on therapy intensity, patient motivation, and active participation. The direct route is through changes in cortical networks through Hebbian(-like) learning and changes in peripheral tissue properties. There is currently mixed evidence for the direct causal effect of robotic assistance on recovery from the upper-limb rehabilitation robotics literature. However, evidence from the neuromuscular electrical stimulation literature provides some support for this causal role. Based on the data at hand, we hypothesize that the enhanced movement-related sensory feedback from robotic assistance has a direct, possibly small, causal role in the sensorimotor recovery of the upper-limb, and this effect might be detectable with high-intensity therapy. Large, high-intensity, controlled studies are warranted to support or refute the role of robotic assistance on recovery, which is both scientifically and practically important.

Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.

Neuroprotective strategies for stroke remain inadequate. Nanoliposomes comprised of phos-phatidylcholine, cholesterol and monosialogangliosides (NL) induced an antioxidant protective response in endothelial cells exposed to amyloid insults. We tested the hypotheses that NL will preserve SH-SY5Y neuroblastoma cell viability following hypoxic injury and will reduce injury in mice following middle cerebral artery occlusion (MCAO). Neuroblastoma were exposed to 20-hour physoxic (5% oxygen) or hypoxic (1% oxygen) condition without or with NL (100 or 300 µg/mL). Viability was measured using calcein-AM fluorescence and SH-SY5Y gene expression of antioxidant proteins heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1) and superoxide dismutase 1 (SOD1) were measured by quantitative polymerase chain reaction. C57BL/6J mice were treated with saline (N=8) or NL (10000 ug/mL, N=7) while undergoing 60-minute MCAO followed by reperfusion. Day 2 post-injury neurologic impairment score and infarction size were compared. Neuroblastoma showed reduced viability following hypoxia that was reversed by NL. NL increased gene expression of HO-1, NQO1 and SOD1 versus controls. NL-treated mice showed reduced neurologic impairment and brain infarct size (18.8±2% versus 27.3±2.3%, p=0.017) versus controls. NL reduced stroke injury in mice subjected to MCAO likely through induction of an antioxidant stress response. NL is a candidate novel agent for stroke.

Background. Epidemiological and clinical studies demonstrated that excessive salt intake causes severe hypertension and exacerbated organ derangement such as chronic kidney disease (CKD). In this study, we focused on evaluating histological and gene-expression findings in the kidney using stroke-prone spontaneously hypertensive rats (SHRSP) with high-salt intake and thromboxane A2/ prostaglandin H2 receptor (TPR) blocker ONO-8809. Methods. SHRSP aged 6 weeks were divided into three groups eating normal chow containing 0.4% NaCl, 2.0%NaCl, or 2.0%NaCl +ONO-8809 (0.6mg/kg p.o. daily). Histological analyses with immunohistochemistry and a gene-expression assay with a DNA kidney microarray were performed after 8 weeks. Results. The following changes were observed with high-salt intake. Glomerular sclerotic changes were remarkably observed in the juxtaglomerular cortex areas. ED1, MCP-1, nitrotyrosine, and HIF-1α staining areas were increased in the glomeruli and interstitial portion. Tbxa2r which encodes TPR, Prcp, and Car7 were significantly underexpressed in the kidney. The plasma 8-isoprostane level was significantly elevated, and was attenuated with ONO-8809 treatment. Conclusion. TXA2 and oxidative stresses exaggerated renal dysfunction in salt-loading SHRSP, and ONO-8809 as a TPR blocker suppressed these changes. Therefore, ONO-8809 is a candidate drug to prevent CKD for hypertensive patients associated with high-salt intake.

This study used established biomarkers of death due to ischemic stroke (IS) and performed network, enrichment, and annotation analysis. Protein-protein interaction (PPI) network analysis revealed that the backbone of the highly connective network of IS death consisted of IL6, ALB, TNF, SERPINE1, VWF, VCAM1, TGFB1, and SELE. Cluster analysis revealed immune and hemostasis subnetworks, which were strongly interconnected through the major switches ALB and VWF. Enrichment analysis revealed that the PPI immune subnetwork of death due to IS was highly associated with TLR2/4, TNF, JAK-STAT, NOD, IL10, IL13, IL4, and TGF-β1/SMAD pathways. The top biological and molecular functions and pathways enriched in the hemostasis network of death due IS were platelet degranulation and activation, the intrinsic pathway of fibrin clot formation, the urokinase-type plasminogen activator pathway, post-translational protein phosphorylation, integrin cell surface interactions, and the proteoglycan-integrin-extra cellular matrix complex (ECM). Regulation Explorer analysis of transcriptional factors shows: a) that NFKB1, RELA and SP1 were the major regulating actors of the PPI network; and b) hsa-mir-26-5p and hsa-16-5p were the major regulating microRNA actors. In conclusion, prevention of death due to IS should consider that current IS treatments may be improved by targeting VWF, VEGFA, proteoglycan-integrin-ECM complex, NFKB/RELA and SP1.

We performed a systematic search and meta-analysis of available literature to determine the safety profile of Cerebrolysin in acute ischemic stroke, filling existing safety information gaps and inconsistent results. We searched EMBASE, PubMed and Cochrane Databases of Systematic Reviews and Clinical Trials up to the end of February 2021. Data collection and analysis was conducted using methods described in the Cochrane Handbook for Systematic Reviews of Interventions. All safety outcomes were analyzed based on risk ratios (RR) and their 95% confidence intervals. The meta-analysis pooled 2202 patients from twelve randomized clinical trials, registering non-statistically significant (p>0.05) differences between Cerebrolysin and placebo throughout main and subgroup analyses. The lowest rate of Serious Adverse Events (SAE), as compared to placebo, was observed for the highest dose of Cerebrolysin (50 mL), highlighting a moderate reduction (RR = 0.6). We observed a tendency of superiority of Cerebrolysin regarding SAE in high dose treatment courses for moderate-severe ischemic stroke, suggesting some effect of the agent against adverse events. This comprehensive safety meta-analysis confirms the safety profile for patients treated with Cerebrolysin after acute ischemic stroke, as compared to placebo.

Adult neurogenesis is an evolutionary conserved process occurring in all vertebrates. However, striking differences are observed between the taxa, considering the number of neurogenic niches, the neural stem cell (NSC) identity and brain plasticity under constitutive and injury-induced conditions. Zebrafish has become a popular model for the investigation of the molecular and cellular mechanisms involved in adult neurogenesis. Compared to mammals, the adult zebrafish displays a high number of neurogenic niches distributed throughout the brain. Furthermore, it exhibits a strong regenerative capacity without scar formation or any obvious disabilities. In this review, we will first discuss the similarities and differences regarding (i) the distribution of neurogenic niches in the brain of adult zebrafish and mammals (mainly mouse) and (ii) the nature of the neural stem cells within the main telencephalic niches. In the second part, we will describe the cascade of cellular events occurring after telencephalic injury in zebrafish and mouse. Our study clearly shows that most early events happening right after the brain injury are shared between zebrafish and mouse including cell death, microglia and oligodendrocyte recruitment, as well as injury-induced neurogenesis. In mammals one of the consequences following an injury is the formation of a glial scar that is persistent. This is not the case in zebrafish, which may be one of the main reasons that zebrafish display a higher regenerative capacity.

Robot-assisted gait training (RAGT) is a promising treatment for stroke rehabilitation. Although the coordination between the upper and lower limbs is important for locomotor training, commercially available robotics for gait training mainly focus on the restoration of lower limb function. We aimed to evaluate the feasibility and usability of complex upper and lower limb RAGT in stroke patients using the GTR-A®, end effector-type robotic device. Patients with subacute stroke (N=9) received 30-minute RAGT thrice a week for two weeks (six sessions). Functionally, the hand grip strength (HGS), Functional Ambulatory Categories, modified Barthel Index, muscle strength test sum score, Berg Balance Scale, Timed Up and Go test, and Short Physical Performance Battery were used. The heart rate and a structured questionnaire were used to evaluate cardiorespiratory fitness and the usability of RAGT. Among the nine patients, all functional parameters between the baseline and post-training were significantly improved after RAGT, except for HGS and the muscle strength test. The questionnaire’s mean scores for each domain were as follows: safety 4.40±0.35, effects 4.23±0.31, efficiency 4.22±0.77, and satisfaction 4.41±0.25. The GTR-A® is a feasible and safe robotic device for patients with gait impairment after stroke. It showed functional improvement with endurance training effects.

Astrocytes are essential for normal brain development and functioning. They respond to brain injury and disease through a process referred to as reactive astrogliosis, where the reactivity is highly heterogenous and context dependent. Reactive astrocytes are active contributors to brain pathology and can exert beneficial, detrimental, or mixed effects following brain insults. Transforming growth factor-β (TGF-β) has been identified as one of the key factors regulating astrocyte reactivity. Genetic and pharmacological manipulation of TGF-β signaling pathway in animal models of CNS injury and disease alters pathological and functional outcomes. This review aims to provide recent understanding regarding astrocyte reactivity and TGF-β signaling in brain injury, aging, and neurodegeneration. Further, it explores how TGF-β signaling modulates astrocyte reactivity and function.

ABSTRACT Background: Nearly two-thirds of acute stroke patients have dysphagia. Dysphagia defined as difficulty in swallowing of liquids or food, vary in severity with symptoms ranging from mild throat discomfort to inability to eat. It’s well known that dysphagia is associated with aspiration pneumonia, dehydration, malnutrition, prolonged length of stay, and increased mortality. Early screening reduces pneumonia rates in stroke and it is usually performed by nurses. Dysphagia screening is recommended but no protocol or tool is pointed.Aim: the aim of this study is to conduct a literature review of dysphagia screening for stroke patient Methods: Literature search three databases (Scopus, Proquest, and Science Direct), with the keywords "Dysphagia" AND "Stroke" AND "Nursing", published in English between 2019 and 2021. Result: Twenty five publications relating to dysphagia screening met the inclusion criteria. There are five methods of dysphagia screening performed by nurses or other health workers: 1) a simple Questionnaire Test (4QT) method, which is by asking the following four questions: does the patient cough or choke while eating or drinking; whether the patient takes longer than usual to eat; does the patient change the thickness of the food to be able to swallow, and whether the voice turns hoarse after eating or drinking; 2) Water Swallow Test (WST) method; 3) Bed Side Screening Tool for Dysphagia (BSTD) method; 4) Volume Viscosity Swallow Test (V-VST) method, namely modification of feeding with first pudding, nectar and finally water; 5) Simplified Cough Test Method. The five screening methods for dysphagia above have been tested for sensitivity and specificity, as well as positive and negative predictive valuesConclusion: screening is a first step in the identification of swallowing impairment or dysphagia of stroke patient. Dysphagia is an independent predictor of poor patient outcome and prolonged recovery time. Nurse has an important role to conduct a screening and must ensure that the selected tools has high reliability and concurrent validity. Key Words: Stroke, Dysphagia, Screening, Nursing

(1) Background; limited research exists which considers master plots expressed by individuals with Stroke. The literature so far has focused on identified pre-established illness narrative types; (2). Methods: A narrative method was selected and a purposive sample of individuals with Stroke are identified. A categorical-form analysis was undertaken; (3) Results: A narrative master plot named overcoming the monster is identified and explored for its components and located temporally for each participant; (4) Conclusions: Health care professionals need to understand the importance of understanding the master plot overcoming the monster. This research supports the need for health care professionals to recognise and support narratives by listening in a non-directive way.

Stroke represents one of the most important causes of morbidity ( eighty million patients with disabling of ongoing effects of stroke at a given time, globally) and mortality (the second leading cause of death) worldwide. Innovative systems biology-based approach is likely to increase the understanding of the underpinning of acute stroke promise to enhance stroke prevention, acute treatment, and neurorehabilitation. Recent growing body of evidence with shared pathobiology with COVID-19 and the critically important role of inflammation in the context of stroke points to far-reaching consequences of acute stroke, just as in the case of COVID-19 ( post-acute event issues as well as long term issues ) . So far, stroke typically defined by late-appearing disease manifestation by the range of stroke subtypes as defined by the WHO or American Stroke Association. This definition neglects the underlying pathobiological mechanisms such as low-grade chronic inflammation and already compromised vascular system. Diseases such as stroke is hardly a simple result of a single problem, but rather a complex cascade of pathobiological processes and interactions in a complex biochemical environment. The evidence of changes in innate immunity and adaptive immunity during the index event of acute stroke and recovery over next 3-12 months can be easily elicited with simple bedside blood tests such as neutrophil-lymphocyte ratio (NLR) with well over 300 published papers including several systematic reviews and meta-analyses confirming this. Global standard operating procedures (SOP) of stroke care dictated by the national and international stroke guidelines at present. It is imperative to explore the evidence of systems biology approach in current stroke guidelines. This is likely to be a key turning point in managing stroke across the continuum (prevention, management of acute event and rehabilitation).

This study aimed to analyze the responsiveness of the 5STS test among stroke patients and to estimate the MCIDs for different severity levels of community ambulation and stages of recovery. The 5STS and comparator instruments [gait speed and Functional Ambulatory Category (FAC)] were evaluated at baseline. These measures were repeated at 4 (Stage 1) and 8 weeks (Stage 2), together with the Global Rating of Change (GROC). The MCIDs were calculated with two anchor-based methods using the GROC as the external criterion. Responsiveness to change for the 5STS was estimated analyzing the correlation with changes in the two comparator instruments and their capacity to discriminate improvement. For the 5STS test, while the MCIDs of the limited community ambulators were similar in the two stages (around 3 s), those of the household ambulators decreased from 1.9 s to 0.72 s. Spearman's rho coefficients showed an acceptable correlation between changes in 5STS and changes for both the FAC and gait speed changes in both stages of recovery. Our study revealed that the 5STS is responsive to functional changes in patients with stroke and that their degree of severity and stage of recovery influence the MCID values of the 5STS.

Ischemic stroke is one of the most disabling diseases and a leading cause of death globally. Despite advances in medical care, the global burden of stroke continues to grow, as no effective treatments to limit or reverse ischemic injury to the brain are available. However, recent preclinical findings have revealed the potential role of transient receptor potential cation 6 (TRPC6) channels as endogenous protectors of neuronal tissue. Activating TRPC6 in various cerebral ischemia models has been found to prevent neuronal death, whereas blocking TRPC6 enhances sensitivity to ischemia. Evidence has shown that Ca2+ influx through TRPC6 activates cAMP response element-binding protein (CREB), an important transcription factor linked to neuronal survival. Additionally, TRPC6 activation may counter excitotoxic damage resulting from glutamate release by attenuating the activity of NMDA receptors of neurons by posttranslational means. Unresolved though, are the roles of TRPC6 channels in non-neuronal cells such as astrocytes and endothelial cells. Moreover, TRPC6 channels may have detrimental effects on the blood-brain barrier, although their exact role in neurovascular coupling requires further investigation. This review discusses evidence-based cell-specific aspects of TRPC6 in the brain to assess the potential targets for ischemic stroke management.

The clinical interaction between stroke and periodontitis has been consistently studied and confirmed. Hence, forecasting potentially new protein interactions in this association using bioinformatic strategies presents potential interest. In this exploratory study, we conducted a protein-protein network interaction (PPI) search with documented encoded proteins for both stroke and periodontitis. Genes of interest were collected via GWAS database. The STRING database was used to predict the PPI networks, first in a sensitivity purpose (confidence cut-off of 0.7), and then with a highest confidence cut-off (0.9). Genes over-representation was inspected in the final network. As a result, we foresee a prospective protein network of interaction between stroke and periodontitis. Inflammation, pro-coagulant/pro-thrombotic state and ultimately atheroma plaque rupture is the main biological mechanism derived from the network. These pilot results may pave the way to future molecular and therapeutic studies to further comprehend the mechanisms between these two conditions.

The last two decades have witnessed a surge in investigations proposing stem cells as a promising strategy to treat stroke. Since growth factor release is considered as one of the most important aspects of cell-based therapy, stem cells over-expressing growth factors are hypothesized to yield higher levels of therapeutic efficiency. In pre-clinical studies of the last 15 years that were investigating the efficiency of stem cell therapy for stroke, a variety of stem cell types were genetically modified to over-express various factors. In this review we summarize the current knowledge on the therapeutic efficiency of stem cell-derived growth factors, encompassing techniques employed and time points to evaluate. In addition, we discuss several types of stem cells, including the recently developed model of epidermal neural crest stem cells, and genetically modified stem cells over-expressing specific factors, which could elevate the restorative potential of naive stem cells. The restorative potential is based on enhanced survival/differentiation potential of transplanted cells, apoptosis inhibition, infarct volume reduction, neovascularization or functional improvement. Since the majority of studies have focused on the short-term curative effects of genetically engineered stem cells, we emphasize the need to address their long-term impact.

Neural tissue engineering, nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system (CNS) repair. It is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes, making development of CNS therapeutics challenging. Given the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society, it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury levels. Extracellular vesicles (EVs), also known as exosomes, when derived from mesenchymal stem cells, are one of the most promising approaches that have been attempted thus far, as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell transplantation. At the same time, advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur, as well as the release of biomolecules facilitating or inducing the reparative processes. This review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable hydrogels. The rationale behind this hypothesis is presented, analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the brain. This sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration occur. Finally, the importance of including non-human primate (NHP) models in the clinical translation pipeline, as well as the added benefit of multi-modal neuroimage analysis to establish non-invasive, in vivo, quantifiable imaging-based biomarkers for CNS repair are discussed, aiming for more effective and safe clinical translation of such regenerative therapies to humans.

Coronavirus disease 2019 restrictions impacted Canadians' daily living, especially those at higher risk of compromised health conditions. This study aimed to describe the physical, psychological, and social well-being of adults with disabilities, and older adults from May to June 2020. An online survey was used to administer standardized measures of mobility, anxiety and depression, boredom, resilience, technology readiness, social support, social networks, and participation. Seventy-two participants were recruited, with a mean age (SD) of 61.2 (13.8). 69.4% of participants had a disability, and 51.4% were older adults. 27.8% and 16.7% of participants exceeded the anxiety and depression cut-off scores, respectively. Boredom and restriction in participation were experienced by 76.4% and 80.1% of participants, respectively. Participants' mean (SD) resilience and life space scores were 72.4 (14.0) and 51.9 (24.0), respectively. Individuals with disabilities have comparatively higher mean anxiety (5.5 to 3.3), depression (4.8 to 2.9), and boredom (92.2 to 72.3) scores than those without. Individuals with a disability had lower resilience (69.9 to 78.0) and felt more life space restrictions (45.4 to 67.6). Our findings revealed issues with anxiety, boredom, participation, and life space activity. This information may provide supporting evidence when creating policies to mitigate existent health and social inequities.

There is an urgent need to better understand the mechanisms involved in scar formation in brain. It is well known that astrocytes are critically engaged in this process. Here we analyze in-cipient scar formation one week after a discrete ischemic insult to the cerebral cortex. We show that the infarct border zone is characterized by pronounced changes in the organization and subcellular localization of the major astrocytic protein AQP4. Specifically there is a loss of AQP4 from astrocytic endfoot membranes that anchor astrocytes to pericapillary basal laminae and a disassembly of the supramolecular AQP4 complexes that normally abound in these membranes. This disassembly may be mechanistically coupled to a downregulation of the newly discovered AQP4 isoform AQP4ex. AQP4 has adhesive properties and is assumed to facilitate astrocyte mo-bility by permitting rapid volume changes at the leading edges of migrating astrocytes. Thus, the present findings provide new insight in the molecular basis of incipient scar formation.

Interdisciplinary research into the underlying neural processes of music therapy (MT) and subjective experiences of patients and therapists are largely lacking. The aim of the current study was to assess the feasibility of newly developed procedures (including EEG/ECG hyperscanning, synchronous audio-video monitoring, and qualitative interviews) to study the personal experiences and neuronal dynamics of moments of interest during MT with stroke survivors. The feasibility of our mobile set-up and procedures as well as their clinical implementation in a rehabilitation centre and an acute hospital ward were tested with four phase C patients. Protocols and interviews were used for the documentation and analysis of the feasibility. Recruiting patients for MT sessions was feasible, although data collection on three consecutive weeks was not always possible due to organisational constraints, especially in the hospital with acute ward routines. Research procedures were successfully implemented, and according to interviews, none of the patients reported any burden, tiredness or increased stress due to the research procedures, which lasted approx. 3 hours (ranging from 135min to 209min) for each patient. Implementing the research procedures in a rehabilitation unit with stroke patients was feasible and only small adaptations were made for further research.

Photothrombotic stroke (PTS) stimulates the level of N- and C-terminal fragments of Amyloid precursor protein (APP) growth in the cytoplasm of ischemic penumbra cells not earlier but at 24 hours. Here we have shown that APP fragments are visualized in thin unmyelinated fibers of neurons, in containing mitochondria large fibers and in synapses but absent in the nuclei. At 24 hours after PTS, some elements of the destroyed tissue accumulated a significant amount of APP protein. The level of ADAM10 α-secretase decreased on the first day after PTS in the rat brain cortex and ADAM-10 co-localized with the lipid raft marker caveolin-1. PTS caused no changes in the level of β-secretase BACE1 either on the first day after PTS or in the early recovery period. The expression of proteins of the γ-secretase complex: presenilin-1 and nicastrin increased in astrocytes, but not in penumbra neurons after PTS. The β-secretase inhibitor LY2886721 did not affect the infarct size of the mouse cerebral cortex and the level of apoptosis of cells in the perifocal region after PTS. Whereas the inhibitor of γ-secretase DAPT reduced the expression of glial fibrillary acidic protein (GFAP) in astrocytes, prevented the growth of apoptosis of mouse cerebral cortex cells reducing the infarct volume on the 7th and 14th days after PTS. DAPT may be considered as a drug for stroke therapy.

Background: Evaluating muscle mass and function among stroke patients is important. However, evaluating muscle volume and function is not easy due to the disturbance of consciousness and paresis. Temporal muscle thickness (TMT) has been introduced as a novel surrogate marker for muscle mass, function, and nutritional status. We herein performed a narrative literature review on temporal muscle and stroke to understand the current meaning of the TMT in the clinical stroke practice. Methods: The search was performed in PubMed, last updated in October 2021. Report on temporal muscle morphomics and stroke-related diseases or clinical entities were collected. Results: Four studies reported on TMT and subarachnoid hemorrhage, 2 intracerebral hemorrhage, 2 ischemic stroke, 2 standard TMT values, and 2 nutritional status. TMT was reported as a prognostic factor for several diseases, surrogate markers for skeletal muscle mass, and an indicator of nutritional status. Computed tomography, magnetic resonance imaging, and ultrasonography were used to measure TMT. Conclusions: TMT is gradually used as a prognostic factor of stroke or surrogate marker for skeletal muscle mass and nutritional status. Establishing standard methods to measure TMT and large prospective studies to investigate the further relationship between TMT and diseases are needed.

Background: Acute ischemic stroke is among the main causes of mortality worldwide; a rapid and opportune diagnosis is crucial to improve a patient's outcome. MicroRNAs are quite useful for a rapid and accurate diagnosis.Methods: We perform both structural networks approach and a meta-analysis (using a random-effect model to evaluate the heterogeneity and risk bias, according to the PRISMA statement) to analyze the feasibility to develop a microRNA-based biomarker panel for an opportune AIS diagnosis. Results: Structural networks identify a set of eight miRNAs (miR-16, miR-124-3p, miR-484, miR-15a, miR-4454, miR-107, miR-125b-5p and miR-320b) as preliminary microRNA-based biomarker panel, from these only three microRNAs are significantly associated with the main risk factors of AIS, (miR-107: hypertension, 95% CI 9.74-53.24 p<0.0001, type 2 Diabetes mellitus, 95% CI 2.18-19.26); p=0.0008; miR-16 hypertension, 95% CI 1.26-3.56 p=0.0046, smoking, 95% CI 1.07-3.54 p=0.0277; and miR-15a hypertension, 95% CI 1.26-3.56 p=0.0046; smoking, 95% CI 1.07-3.54 p=0.0277). However, the meta-analysis reveals that data is highly heterogeneous and biased; and only microRNAs isolated from plasma samples and further processed in microarrays are the most reliable to distinguish AIS patients.Conclusions: Together our results show that although there are some miRNAs that seem to be associated with AIS, we are still far to develop a miRNA-based biomarker for AIS diagnosis and it is necessary to harmonize the protocols, results and include more populations for further studies otherwise we will remain throwing punches in the dark.

Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.

Objectives To delineate the features of ischemic stroke patients and their caregivers that may predict distress, depression, and anxiety symptoms in the caregivers. Methods The Hospital Anxiety and Depression Score (HADS), Zarit Burden Interview (22 item-ZBI), and Perceived Stress Scale (PSS-10) were used to assess caregivers' burden, stress, depressive, and anxiety symptoms. We performed partial least square-structural equation modeling (PLS-SEM) in order to delineate a multi-step mediation model.Results In this study, 97 stroke patients and their caregivers were included. Multiple regression analysis revealed that ZBI-personal strain and stroke of other determined etiology explained 15.0 percent of the variance in the HADS depression score (p=0.001). We discovered that the caregiver's underlying disease and the National Institute Stroke Score (NIHSS) of the patients explained 13.6 percent of the variance in the total ZBI score of the caregivers (p=0.001). The total ZBI score, the presence of lacunar circulation infarction in the patients, and the caregiver's underlying disease explained 40.9 percent of the variance in the total PSS score of the caregivers (p <0.001). Moreover, PLS analysis showed that the NIHSS and the caregiver's underlying disease had significant indirect effects on the HADS score which were mediated by the ZBI score. Conclusions A large part of the variance in stress and depressive scores in caregivers of ischemic stroke patients is determined by the patient's disability, dependency, cognition, and stroke phenotypes, as well as the caregiver's health status and burden. Screening for the aforementioned factors in ischemic stroke caregivers is critical.

The most important predictors for outcomes after ischemic stroke, that is, for health deterioration and death, are chronological age and stroke severity; gender, genetics and lifestyle / environmental factors also play a role. Of all these, only the latter can be influenced after the event, even though recurrent stroke may be prevented by antiaggregant/anticoagulant therapy, angioplasty of high-grade stenoses, and treatment of cardiovascular risk factors. Moreover, blood cell composition and protein biomarkers such as C-reactive protein or interleukins in serum are frequently considered as biomarkers of outcome. We surveyed protein biomarkers that were reported to be predictive for outcome after ischemic stroke, specifically considering biomarkers that predict long-term outcome (≥3 months) and that are measured over the first days following the event. We classified the protein biomarkers as immune‑inflammatory, coagulation-related, and adhesion-related biomarkers. Some of these biomarkers are closely related to cellular senescence and, in particular, to the inflammatory processes that can be triggered by senescent cells. Moreover, the processes that underlie inflammation, hypercoagulation and cellular senescence connect stroke to cancer, and biomarkers of cancer-associated thromboembolism, as well as of sarcopenia, overlap strongly with the biomarkers discussed here. Finally, we demonstrate that most of the outcome-predicting protein biomarkers form a close-meshed functional interaction network, suggesting that the outcome after stroke is partially determined by an interplay of molecular processes relating to inflammation, coagulation, cell adhesion and cellular senescence.

Non-pharmacologic options like the ketogenic diet (KD) and intermittent fasting (IF) are practical nutritional interventions with minor reported side effects like gastrointestinal symptoms, dyslipidemia, and hypomagnesemia for various medical ailments. In conjunction with IF, KD shows promise in weight loss, diabetes management, cardiovascular disorders, polycystic ovarian syndrome, cancer, and chronic neurological disorders. Based on prior research, we have examined the mechanism of action of KD and IF and their effect on neurological diseases, cancer, and obesity. We have also suggested evidence-based recommendations for the safer practice of KD and IF. Despite potential benefits, long-term adherence to KD poses challenges. Periodic KD implementation may thus benefit newly diagnosed overweight or obese patients with type 2 diabetes mellitus, aiding blood glucose and lipid management while promoting weight loss. KD is a high-fat and low-carbohydrate diet with a ratio of fat to carbohydrates and protein being 4:1 or 3:1, and thus, for peripheral tissues and the brain, fatty acids become the mandatory source of cellular energy. Ketone bodies have been used as the primary energy source during fasting. KD has been utilized as an effective treatment for refractory epilepsy since the 1920s. Evidence of the neuroprotective role of KD in diseases like epilepsy, stroke, traumatic brain injury, Alzheimer’s disease, and other neurological diseases has been noted. Since the 1960s, KD has become a popular method for obesity treatment. In addition, KD has been suggested as a potent anticancer therapy when used alone or as an adjuvant. KD may increase tumor cell sensitivity when combined with classic chemotherapy and radiotherapy. Thus, the probability that modifying the diet can help manage obesity, cancer, and chronic neurological disease without depending on pharmacological treatment and their serious side effects for a lifetime is promising and requires further investigation. KD holds promise as a potential adjunctive therapy in various neurological disorders, offering new avenues for treatment and neuroprotection. IF has shown potential in slowing the progression of neurodegenerative diseases such as Alzheimer's and Parkinson's by promoting antioxidant defense and suppressing inflammation. KD and IF show promise in cancer therapy by targeting altered cancer cell metabolism. Additionally, KD may enhance the effects of standard treatments like chemotherapy and radiotherapy. Some of the most robust reports of keto's possible benefits have come from glioblastoma, a very aggressive brain cancer. KD has also shown strong evidence for its effectiveness in weight loss, mainly attributed to its appetite-suppressing action in ketosis. However, long-term adherence to KD can be challenging, and periodic KDs may help manage blood glucose and lipid levels in overweight or obese patients with type 2 diabetes mellitus. Likewise, IF may be more effective than regular calorie restriction for achieving weight loss goals when combined with exercise programs. More prospective human studies are warranted to evaluate both KD and IF's potential therapeutic effectiveness and safety.

A recent systematic review for 19 selected articles after searching through to 30 September 2017 showed vitamin D deficiency was associated with ischemic stroke (IS), not hemorrhagic stroke (HS). But a heterogeneity would be introduced with comparing the lowest and highest category of vitamin D. The aim of this article was to conduct an updated meta-analysis (UMA) with searching through to 31 March 2019. An interval collapsing method as information extraction was applied in order to decrease a heterogeneity among studies. Additional articles were selected from cited lists from 19 selected articles using citation discovery tools. Random effect model was applied if I-squared value was over 50%. A funnel plot and Egger’s test were used to detect a publication bias. After 5 new studies were added, the summary RRs [and their 95% confidence intervals] (I-squared value) were 1.52 [1.33–1.74] (0.0%) in IS, and 2.44 [1.34–4.46] (69.7%) in HS. This UMA supported the hypothesis that serum vitamin D deficiency was associated with an increased risk of HS as well as IS. Diverse public health programs against vitamin D deficiency status would be needed for higher risk group, especially elderly people.

Tremor is a prevalent symptom associated with multiple conditions, including Essential Tremor (ET), Parkinson’s disease (PD), multiple sclerosis (MS), stroke, and trauma. The surgical management of tremor evolved from stereotactic lesions to deep-brain stimulation (DBS), which allowed safe and reversible interference with specific neural networks. This paper reviews the current literature on DBS for tremor, starting with a detailed discussion of current tremor targets (Vim, Raprl, caudal Zi, Vo and STN) and continuing with a discussion of results obtained when performing DBS in the various aforementioned tremor syndromes. Future directions for DBS research are then briefly discussed.

Background: Citicoline, a medical food, lacks proven efficacy for ischemic stroke and has uncertainties around its harms. The continued prescription should be reevaluated given the more robust, high-quality Evidence against that medical food. This essay is based on a recent Cochrane review and uses only one all-cause mortality as the primary outcome. Therefore, the essay should be considered as something other than an updated Cochrane review but like a reflection based on Evidence-based Medicine and Philosophy of Science analysis. Question Research: Why citicoline (a medical food) should not be prescribed to treat people with acute ischemic stroke: The certainty of the Evidence.? Objective: Demonstrate from evidence-based medicine and philosophy of science perspective that citicoline should not be prescribed for acute ischemic stroke due to lack of efficacy and harm uncertainties. Search publications: We searched in PubMed and Cochrane Library from 2020 until 30 October 2023. We, furthermore, used engineering machines Bing and Google Scholar to detect additional papers. Additionally, we also reviewed reference lists of the retrieved publications and review articles and searched the websites of the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA). Selection criteria: We included systematic reviews, meta-analyses, randomized clinical trials, clinical guidelines focused on acute ischemic stroke and comparing citicoline versus placebo or no intervention. We excluded narrative reviews, observational studies and ongoing trials. Data collection and analysis: We identified only new randomized clinical trials and assessed the risk of bias in seven domains. The other eight trials were already included in the mentioned Cochrane review. The systematic reviews with or without meta-analyses were assessed using McMaster University guidelines. We estimated risk ratios (RRs) for that outcome. We measured statistical heterogeneity using the I² statistic. We conducted our analyses using the fixed effect model. We did not use the GRADE approach due to what is shown in a Cochrane review published in 2020 by Martí-Carvajal et al. We used the RevMan 5.4 software from Cochrane Collaboration to conduct the forest plot. We used a Trial Sequential Analysis with Copenhagen Trial Unit Software. We estimated a Bayes factor from the relative risk and 95% confidence interval. Results: We identified only one new RCT (N = 99) reported mortality data and three clinical guidelines. We conducted a new meta-analysis with nine trials (N = 4461) having a high risk of bias and showing little to no difference in mortality between citicoline and placebo (17.1% vs 18.4%; RR 0.94, 95% CI 0.82 to 1.06; I2 = 0%). The Bayes factor was 0.7, indicating weak Evidence for the null over the alternative hypothesis. Trial sequential analysis suggested sufficiency of Evidence for mortality. No guidelines recommend citicoline. Conclusions: This essay reassessed citicoline for acute ischemic stroke after the 2020 Cochrane review. Adding a new RCT further supported the lack of mortality benefit with citicoline. The overall evidence quality could be better. Analyses using evidence-based medicine and philosophy of science approaches do not support prescribing citicoline due to a lack of efficacy substantiation and potential harms.

Stroke often results in impaired gait, which can limit community ambulation and the quality of life. Recent works have shown the feasibility of transcranial Direct Current Stimulation (tDCS) as an adjuvant treatment to facilitate gait rehabilitation. Since the cerebellum plays an essential role in balance and movement coordination, which is crucial for independent overground ambulation, so, we investigated the effects of cerebellar tDCS (ctDCS) on the post-stroke overground gait performance in chronic stroke survivors. Fourteen chronic post-stroke male subjects were recruited based on convenience sampling at the collaborating hospitals where ten subjects finally participated in the ctDCS study. We evaluated the effects of two ctDCS montages with 2mA direct current, a) optimized configuration for dentate stimulation with 3.14cm² disc anode at PO10h (10/5 EEG system) and 3.14cm² disc cathode at PO9h (10/5 EEG system), and b) optimized configuration for leg lobules VII-IX stimulation with 3.14cm² disc anode at Exx8 (electrodes defined by ROAST) and 3.14cm² disc cathode at Exx7. We found ctDCS to be acceptable by all the exposed subjects. The ctDCS intervention had an effect on the 'Normalised Step length Affected side' (p=0.1) and 'Gait Stability Ratio' (p=0.0569), which was found using Wilcoxon signed-rank test at 10% significance level. Also, ctDCS montage specific effect was found using a two-sided Wilcoxon rank-sum test at a 5% significance level for 'Step Time Affected Leg' (p=0.0257) and '%Stance Time Unaffected Leg' (p=0.0376). Moreover, the changes in the quantitative gait parameters across both the montages were found to be correlated to the mean electric field strength in the lobules based on partial least squares regression analysis (R² statistic = 0.6574) where the mean electric field strength at the cerebellar lobules, Vermis VIIIb, Ipsilesional IX, Vermis IX, Ipsilesional X, had the most loading. In conclusion, our feasibility study indicated the potential of a single session of ctDCS to contribute to the immediate improvement in the balance and gait performance in terms of gait-related indices and clinical gait measures.

Achieving neuroprotection in ischemic stroke patients has been a multi-decade medical challenge. Numerous clinical trials were discontinued in futility and many were terminated in response to deleterious treatment effects. Recently however, several positive reports have generated the much-needed excitement surrounding stroke therapy. In this review, we describe the clinical studies that significantly expanded the time window of eligibility for patients to receive mechanical endovascular thrombectomy. We summarize the results available thus far for nerinetide, which can be considered the most promising neuroprotective agent yet for stroke treatment. Lastly, we reflect upon aspects of these successful trials in our own studies targeting the Kv2.1-mediated cell death pathway in neurons for neuroprotection. We propose that recent changes in the clinical landscape must be adapted by preclinical research in order to continue progressing toward the development of efficacious neuroprotective therapies for ischemic stroke.

Despite the relative scarcity of studies focusing on pharmacotherapy in aphasia, there is evidence in the literature indicating that remediation of language disorders via pharmaceutical agents could be a promising aphasia treatment option. Among the various agents used to treat chronic aphasic deficits, cholinergic drugs have provided interesting results. In the current review, we focused on published reports investigating the impact of acetylcholine on language and further cognitive disturbances. It has been suggested that acetylcholine plays an important role in neuroplasticity and is related to several aspects of cognition, such as memory and attention. Moreover, cholinergic input is diffused to a wide network of cortical areas, which have been associated with language sub-processes. This could be a possible explanation for the positive reported outcomes of cholinergic drugs in aphasia recovery, and specifically in distinct language processes, such as naming and comprehension, as well as overall communication competence. However, evidence with regard to functional alterations in specific brain areas after pharmacotherapy is rather limited. Finally, despite the positive results derived from the relevant studies, cholinergic pharmacotherapy treatment in post-stroke aphasia has not been widely implemented. The present review aims to provide an overview of the existing literature in cholinergic pharmacotherapy interventions in post-stroke aphasia, following an integrated approach by converging evidence from neuroanatomy, neurophysiology, and neuropsychology.

Robot-assisted rehabilitation has emerged as a promising approach for enhancing motor function in stroke survivors. However, the feasibility and effectiveness of home-based robotic training in this population are underexplored, especially in low/middle-income countries. This feasibility study aimed to address this gap by examining the feasibility and effectiveness of independent home-based training using PLUTO, a robotic device for hand training. A total of 7 chronic stroke survivors were recruited, with 5 completing the study. The results revealed high engagement and adherence to the home-based training program, with participants averaging 1659.8 minutes of training over 24.8 days. The PLUTO system demonstrated excellent usability and elicited positive user perceptions. Significant improvements were observed in functional outcomes, as evidenced by a noteworthy increase in Fugl-Meyer Assessment scores (mean increase of 6.2 points, exceeding the minimal clinically important difference (MCID) of 5.35 points). Furthermore, participants showed improvements in the ABILHAND measure (mean improvement of 1.24 logits, surpassing the MCID of 0.2 logits) and the Barthel Index (mean increase of 8.8 points). These findings demonstrate the feasibility and effectiveness of home-based robotic rehabilitation for chronic stroke survivors. This has implications for expanding access to rehabilitation services in low- and middle-income countries, enhancing patient engagement and adherence, and improving functional outcomes. Larger controlled studies are warranted to evaluate the effectiveness of home-based robotic rehabilitation programs.

Background: Emergency medical services (EMS) are the first health care contact for the majority of stroke patients. However, there is a lack of data on the current paramedics’ hospital-directed feedback and training needs across different health care settings. We aimed to evaluate paramedics’ prehospital stroke care knowledge, training needs, and current status of feedback on suspected stroke patients. Methods: We surveyed paramedics from the Vilnius region from September to November 2019, and compared the answers between the city and the district agencies. The questionnaire content included questions on paramedics’ demographic characteristics, prehospital stroke care self-assessment, knowledge on stroke mimics, stroke training needs, and the importance of hospital-directed feedback on suspected stroke patients. Results: A total number of 161 paramedics were surveyed, with more district paramedics rating their prehospital stroke care knowledge as inadequate (44.8% (95% confidence interval (CI) 32.8–57.6) vs 28.1% (95% CI 20.1–27.8), p = 0.028). In addition, more district paramedics indicated a need for additional stroke training (83.1% (95% CI 71.5–90.5) vs 69.8% (60.0–78.1), p = 0.043). However, respondents reported being the most confident while dealing with stroke (71.3%, 95% CI 63.8–77.7) compared to other time-critical conditions (p < 0.001). Vertigo (60.8%, 95% CI 53.0–68.0), brain tumours (56.3%, 95% CI 48.5–63.8), and seizures (54.4%, 95% CI 46.7–62.0) were indicated as the most common stroke mimics. Only 6.2% (95% CI 3.4–11.1) of respondents received formal feedback on the outcome of suspected stroke patients brought to the emergency department. Conclusion: A high proportion of paramedics self-perceive having inadequate stroke knowledge and an urgent need for further stroke training. The EMS staff indicate receiving an insufficient amount of feedback on suspected stroke patients, even though the usefulness is perceived to be paramount.

Taking care of stroke survivors can be taxing, however, it was understudied in Malaysia. This study aims to describe the burden of informal stroke caregivers within three months after hospital discharge. A longitudinal study design was conducted. Acute stroke survivors and their informal caregivers were recruited prior to hospital discharge, and the caregivers were interviewed by phone. Self-reported caregiver burdens were measured with Zarit Caregiver Burden Interview – Malay version (MZBI) and Caregiver Assessment of Function and Upset – Malay version (Malay-CAFU). The MZBI and Malay-CAFU scores were collected four times within three months. A total of 85 stroke survivors and 155 informal caregivers were recruited, with 58.1% of the caregivers were female. The stroke survivors had two caregivers on average. The mean (SD) scores for the three scales show a reduction, from 27.42 (12.73) in the first week to 17.77 (11.20) in the third month for MZBI, from 1.14 (0.94) to 0.62 (0.64) for instrumental activities of daily livings (IADL) of Malay-CAFU upset scale and 1.36 (1.00) to 0.78 (0.65) for activities of daily living (ADL) of Malay-CAFU upset scale in the same period. Stroke survivors may have several caregivers, usually their spouses or children. Within a short period, the caregiver’s burden was reduced. Early psychosocial support to alleviate the caregiver burden may be necessary.

Decades of research suggest that Mindfulness-Based Stress Reduction (MBSR) training supports a greater capacity to live with chronic medical conditions and contributes to lowering stress levels. This paper introduces a model for a Mindfulness-Based Recovery from Stroke (MBRfS) for promoting stroke recovery, informed by the lived experience of the author (a stroke survivor and certified MBSR instructor), the research literature regarding MBSR training, and the specific challenges of stroke recovery. Four themes emerged from the autoethnographic analysis that informed the proposed model: Readiness to accept the stroke event and the acquired brain injury; Navigating uncertainties of stroke recovery with awareness and self-responsibility for outcomes; Trusting the inherent wisdom of the body as a stroke recovery “teacher”; and Increased capacity to integrate complex emotions with self-compassion, and a sense of wholeness. A four component MBRfS model is offered, which consists of an integration amongst a modified MBSR framework, emergent attitudinal themes, and insights from the autoethnographic vignettes. The MBRfS model offers a path for providing participants with a supportive experience within stroke recovery. Recommendations and suggestions for future studies are offered to support the development of MBRfS for stroke survivors and their caregivers, as well as contributing to health care providers.

Background: Pharmacologic and non-pharmacologic treatments for stroke are essential but could be costly or harmful whereas probiotic has been a promising alternative. This scoping review aimed to synthesize the in vitro and in vivo evidence of probiotics on stroke-related neurological, biochemical, and histochemical outcomes. Method: We searched in PubMed, Embase, and Cochrane Central Register of Clinical up to May 7, 2021, and screened by two independent reviewers. We included the use of probiotics, prebiotics, and symbiotics both in vitro and in vivo for the prevention or treatment of the stroke-related model. Result: Of 6,293 articles, 4,990 passed the initial screen, of which 36 theme-related full-texts were assessed and 13 were included in this review. Probiotics could ameliorate the neurological deficit and show their property as an anti-inflammation and anti-oxidative stress. Histopathologically decreased loss of cerebral volume and inhibition of neuronal apoptosis were found. Conclusion: There are potential cognitive benefits of probiotic supplementation, especially among animal models, on decreasing cerebral volume, increasing neurological score, and decreasing the inflammatory response. However, further investigation is needed to validate these conclusions in various populations.

BACKGROUND: Acute stroke is a time-critical emergency where diagnosis and acute management are highly dependent upon accuracy of patient’s history. We hypothesised that language barrier is associated with delayed onset time to thrombolysis and poor clinical outcomes. AIM: To evaluate the effect of language barriers on time to thrombolysis and clinical outcomes in acute ischemic stroke. METHODS: This is a retrospective study of all patients admitted to a metropolitan stroke unit (Melbourne, Victoria, Australia) with an acute ischemic stroke treated with tissue plasminogen activator between 1/2013 and 9/2017. Baseline characteristics, thrombolysis time intervals, length of stay, discharge destination, and in-hospital mortality were compared between patients with and without a language barrier using multivariate analysis after adjustment for age, sex, stroke severity, premorbid modified Rankin Scale (mRS) and Charlson Comorbidity Index (CCI). Language barriers were defined as a primary language other than English. RESULTS: A total of 374 patients were included. Of this, 76 patients (20.3%) had a language barrier. Mean age was 5 years older for patients with language barriers (76.7 vs 71.8 years, P=0.004). Less non-English speaking patients had pre-morbid mRS score of zero (P=0.002) and more had pre-morbid mRS score of one or two (P=0.04). There was no statistically significant difference between two groups in terms of stroke severity on presentation (P=0.06). The onset to needle time was significantly longer in patients with a language barrier (188 min vs 173 min, P=0.04). Onset to arrival and door to imaging times were surprisingly similar between the two groups. However, imaging to needle time was 9 minutes delayed in non-English speaking patients with a marginal P value (65 vs 56 min, P=0.06). patients with language barriers stayed longer in stroke unit stay (6 vs 4 days, P=0.02) and had higher rates of discharge to residential aged care facilities in those admitted from home (9.2% vs 2.3%, P=0.02). In-hospital mortality was not different between two groups (P=0.8) CONCLUSION: In this study language barriers were associated with almost 14 min delay in thrombolysis. The delay was mostly attributable to imaging to needle time. Language barriers were also associated with poorer clinical outcomes.

Repeated desaturation of oxyhemoglobin, micro-arousals, which are typical in obstructive sleep apnea syndrome (OSAS), have negative effects on the health of patients, leading to a wide range of complications such as cardiovascular (arterial hypertension, pulmonary hypertension, chronic heart failure, arrhythmias, myocardial infarction) cerebrovascular (strokes), metabolic (insulin resistance, obesity, diabetes mellitus, metabolic syndrome), gastrointestinal (non-alcoholic liver disease), urinary (chronic renal failure), neuropsychiatric complications and a wide range of malignancies. This in turn has a multilateral effect on familial, occupational and social life, as well as increasing the risk of road traffic accidents or accidents at workplace. Awareness, timely screening and prevention of complications play an important role in the diagnosis and treatment of comorbid conditions. This review focuses on comorbidities in OSAS and the effect of CPAP therapy on their prognosis.

Lesion studies are crucial in establishing brain-behavior relationships, and accurately segmenting the lesion represents the first step in achieving this. Manual lesion segmentation is the gold standard for chronic strokes. However, it is labor-intensive, subject to bias, and limits sample size. Therefore, our objective is to develop an automatic segmentation algorithm for chronic stroke lesions on T1-weighted MR images. Methods: To train our model, we utilized an open-source dataset: ATLAS v2.0 (Anatomical Tracings of Lesions After Stroke). We partitioned the dataset of 655 T1 images with manual segmentation labels into five subsets and performed a 5-fold cross-validation to avoid overfitting of the model. We used a deep neural network (DNN) architecture for model training. Results: To evaluate the model performance, we used three metrics that pertain to diverse aspects of volumetric segmentation including shape, location, and size. The Dice similarity coefficient (DSC) compares the spatial overlap between manual and machine segmentation. The average DSC was 0.65 (0.61- 0.67; 95% bootstrapped CI). Average symmetric surface distance (ASSD) measures contour distances between the two segmentations. ASSD between manual and automatic segmentation was 12mm. Finally, we compared the total lesion volumes and the Pearson correlation coefficient (ρ) between the manual and automatically segmented lesion volumes, which was 0.97(p-value &lt; 0.001). Conclusions: We present the first automated segmentation model trained on a large multicentric dataset. This model will enable automated on-demand processing of MRI scans and quantitative chronic stroke lesion assessment.

Background: Substance use continues to be on the rise in the United States and has been linked to new onset cardiovascular (CVDs) and cerebrovascular disorders (CeVDs) leading to hospitalizations. We aimed to study the association of different subtypes of substance use disorders (SUDs) among hospitalized patients, with the different subtypes of CVDs and CeVDs, using the National Inpatient Sample (NIS) Database. Additionally, we aimed to assess the odds of hospitalizations with new onset CVDs and CeVDs among patients with different types of SUDs. Methods: A retrospective study of the NIS database (2016-2017) using the ICD-10-CM codes was performed. The hospitalizations with a secondary diagnosis of SUDs were identified. Weighted univariate analysis using the chi-square test and multivariate survey logistic regression analysis was performed to evaluate for the incidence, prevalence, and odds of association between vascular events and SUDs. Results: There were a total of 58,259,589 hospitalizations, out of which 21.42% had SUDs. Out of all the hospitalized patients between the age 18-50, more patients had SUDs than not (31.83%, p< 0.0001). This difference existed for all the different subtypes of SUDs including alcohol related disorder (42.61%), amphetamine dependence (76.17% vs 31.83%), cannabis related disorder (75.17%), cocaine related disorders (57.87%), hallucinogen related disorder (82.91%), inhalant related disorders (67.25%), opioid related disorders (52.86%), and nicotine dependence (35.72%). We found a significant association of acute ischemic stroke with amphetamine dependence (OR 1.23, 95%CI 1.14-1.33), cocaine related disorders (1.17, 1.12-1.23) and nicotine dependence (1.42, 1.40-1.43). Similarly, the association of intracerebral hemorrhage was higher with amphetamine dependence (2.58, 2.26-2.93), and cocaine related disorders (1.62, 1.46-1.79). The association of subarachnoid hemorrhage was noted to be higher with amphetamine dependence (1.82, 1.48-2.24) and nicotine dependence (1.47, 1.39-1.55). In terms of association of cardiovascular disorders with SUDs,the patients with myocardial infarction had higher odds of nicotine dependence (1.85, 1.83-1.87) than not, Similarly, the patients with angina pectoris were noted to have a higher association with cocaine related disorders (2.21, 1.86-2.62), and those with atrial fibrillation had a higher association alcohol related disorders (1.14, 1.11-1.17). Conclusion: Our study demonstrates the variability of CVD and CeVD in patients hospitalized for SUD. Findings from our study may help promote increased awareness and early management of these events. Further studies are needed to evaluate specific effects of frequency and dose on the incidence and prevalence of CVD and CeVD in patients with SUD.

IntroductionHope is an essential concept for rehabilitation of people with stroke. The current study extended research on the model of emotions, adaptation, and hope (MEAH) by extending it according to a previously established framework of hope.MethodsAn interpretive hermeneutic phenomenological study was conducted. People with stroke living in the community of the West Midlands were included. Physiotherapy students received training as part of a research placement to deliver a single intervention session using an extended version of the MEAH. Content analysis of the responses to the MEAH were taken and a process evaluation was undertaken in the form of a semi-structured interview after the intervention.ResultsSeventeen individuals (70.1±12.2 years) with stroke were included. Results considered the responses to the MEAH as a therapeutic driver and a process evaluation from people with stroke that undertook the intervention. Important scoring differences were noted for those who could and those who were not able to set goals. The MEAH tool appeared to be one way to help develop goals for people with stroke in a personalised way, however the value of the tool was identified by those who did not set a goal. Positive experiences of the intervention were reported across all people with stroke.DiscussionThe MEAH tool may be one way to support stroke rehabilitation and enhance the therapeutic encounter between physiotherapists and people with stroke.

Background & Motivation: Stroke outcomes following revascularization therapy (intravenous thrombolysis, IVT, and/or mechanical thrombectomy, MT) depend critically on time from stroke onset to treatment. Different service configurations may prioritise time to IVT or time to MT. In order to evaluate alternative acute stroke care configurations, it is necessary to estimate clinical outcomes given differing times to IVT and MT. Method: Model using an algorithm coded in Python. This is available at https://github.com/MichaelAllen1966/stroke_outcome_algorithm. Results: We demonstrate how the code may be used to estimate clinical outcomes given varying times to IVT and MT. Conclusion: Python code has been developed and shared to enable estimation of clinical outcome given times to IVT and MT. Here we share pseudocode and links to full Python code.

In former times, the spinal cord was considered a hard-wired network for spinal reflexes and a conduit for long-range connections. This view has changed dramatically over the past few decades. It is now recognized as a plastic device whose structures and functions adapt to changing circumstances. While such changes also occur under physiological conditions, the most dramatic alterations take place during or after various pathological events. It is astonishing what mechanisms the musculo-skeletal system has evolved to come to grips with the damages. Many of these changes are maladaptive, but some appear to help adapt to the new conditions. Although myriads of studies, using manifold methods, have been devoted to elucidating the underlying mechanisms, in humans and animal models, the etiology and pathophysiology of various diseases are still little understood, due to a number of reasons. We will here try to summarize some results and remaining problems in a selection of diseases, in particular spinal muscular atrophy (SMA), amyotrophic laterals sclerosis (ALS), and predominantly spinal cord injury (SCI) with occasional relations to stroke. Especially the changes in SCI (and stroke) depend on the cause, site and extent of the afflicted damage and are therefore multifarious. At the end, we will briefly summarize results indicating that operant, classical and instrumental conditioning can be used to produce plastic changes in healthy people, with potentials for applications to patients with spinal cord injury. In order not to overload the article, we will not delve deeply into sub-cellular processes.

Background: Hypereosinophilic syndromes (HES) are a group of relatively rare disorders in which neurological manifestations are not uncommon including ischemic stroke. The hypothesized pathophysiological mechanisms are hypercoagulability, cardioembolism (mainly mediated by myocardial involvement) and damage to the endothelium. A variable ischemic pattern has been described, including an association of territorial and border zone ischemic stroke. Methods: Three patients who presented to our department with acute stroke were selected aiming to show these three different mechanisms inferred from the stroke pattern on brain Magnetic Resonance Imaging (MRI) and to simultaneously illustrate the three main causes of HES. Results and Discussion: The first patient is a 55-year-old man with an abrupt onset of aphasia due to an acute ischemic stroke involving the left parietal lobule and the angular gyrus; recent lab test had shown hypereosinophilia. An extensive workup excluded primary and secondary causes of hy-pereosinophilia so a diagnosis of idiopathic hypereosinophilia was formulated and he was treated with high doses of steroids. The second patient had severe hypereosinophilia and developed multiple small scattered ischemic lesions, mainly in watershed zones. The history of severe asthma and recurrent sinusitis supported the diagnosis of EGPA (Eosinophilic Granulomatosis with Polyangiitis); considering the severe clinical conditions and the presumptive role of hypereo-sinophilia in determining her symptoms, steroid treatment was promptly started, with good clinical response. The third patient also presented with multiple metachronous ischemic lesions, both in cortical and watershed distribution and marked eosinophilia; the diagnostic work-up found an ovarian cancer. She was treated with steroids and then underwent surgery and adjuvant chemotherapy. Conclusions: HES should be considered in stroke etiological evaluation, although it is a rare disorder, and border zones pattern on neuroimaging is quite suggestive. A thorough research of the sources of hypereosinophilia should be performed to select the appropriate therapy.

Background: Anemia is one of the most frequent diseases worldwide, affecting a third of the general population. Anemia in general and in particular, iron-deficient anemia (IDA), has been associated to a higher risk of thrombotic manifestations, including ischemic stroke and cerebral venous thrombosis (CVT), as well as systemic extra cerebral arterial and venous thrombosis. Despite these data, anemia is seldom considered as an etiological factor of stroke. Methods: An individual case encompassing all known neurovascular and systemic arterial and venous thrombotic manifestations related to IDA is presented with the focus on clinical reasoning issues in the diagnostic pathways, starting from the neuroradiological signs. The main questions have been identified and addressed in a narrative review of the most relevant data in the literature from a pragmatic and clinical viewpoint. Results and Discussion: The presented case concerns a 46 years old man admitted to the Stroke Unit because of acute is-chemic stroke with multiple thrombi in large intracranial and extracranial vessels, multifocal ischemic lesions in several arterial territories and the concurrent finding of asymptomatic CVT, pulmonary embolism with lung infarction and aortic thrombosis. An extended diagnostic work-up excluded the main etiologies (arterial dissection, cardiac embolism, genetic and acquired prothrombotic disorders, as cancer and antiphospholipid syndrome), except for a severe IDA, such as to require blood transfusions followed by anticoagulant therapy for the several thrombotic manifestations. Neuroimaging and systemic vascular findings have been analyzed and the main issues proposed by the case in the diagnostic pathway have been identified and discussed in a pragmatic clinical road map reviewing the data provided by the literature. Conclusions: IDA is a common but treatable condition that, independently or synergically, may increase the risk of thrombotic events. The diagnostic and therapeutic approach has not yet defined and each case should be individually addressed in a pragmatic clinical road map.

The observation of persons in the acute phase of ischemic stroke (IS) allowed to select a group of patients whose spontaneous motor activity stood out from the typical clinical picture of the hemiplegia syndrome. It has been noticed that these persons have presented tendency to shift the body weigh toward more affected side and the tendency to move the upper and / or the lower limb (not covered by the neurological syndrome) in simple, repetitive patterns. The purposes of this study were: to define noted kind of behavior, and to select symptoms which can predict the occurrence it. Persons (n=222) hospitalized due to first-time IS were as-signed to 3 groups. A: 78 persons with no lateralization of the neurological syndrome (LoNS). B: 109 persons with LoNS, O+: 35 persons, who at the beginning of hospitalization presented, apart from LoNS, charac-teristic motor symptoms. Persons underwent therapy depending on the neurological symptoms. If the pa-tient demonstrated the potential symptoms for overactivity of the less affected side (OLAS), to confirm it, trial therapy was performed. The predictive symptoms, selected among these from the index day, for the occurrence OLAS in sitting were distinguished: asymmetry in supine and simple, repetitive movements of nonparetic upper extremity.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

Background: There is an increasing interest in the role of EEG in neurorehabilitation. We primarily aimed to identify the knowledge base through highly influential studies. Our secondary aims were to imprint the relevant thematic hotspots, research trends, and social networks within the scientific community. Methods: We performed an electronic search in Scopus looking for studies reporting on rehabilitation in patients with neurological disabilities. The most influential papers outlined the knowledge base, while a word co-occurrence analysis imprinted the research hotspots. Likewise, co-citation analyses highlighted collaboration networks between Universities, authors, and countries. The results were presented in summary tables, burst detection plots, and geospatial maps. Finally, a content review based on the top-20 most cited articles completed our study. Results: Our current bibliometric study was based on 874 records from 420 sources. There was a vivid research interest in EEG use for neurorehabilitation, with an annual growth rate as high as 14.3%. The most influential paper was the study titled "Brain-computer interfaces, a review" by Nicolas-Alfonso LF and Gomez-Gill J, with 997 citations, followed by "Brain-computer interfaces in neurological rehabilitation" by Daly J. and Wolpaw JR (708 citations). The USA, Italy, and Germany were among the most productive countries. The research hotspots shifted with time from the use of “functional magnetic imaging” to EEG-based “brain-machine interface”, “motor imagery”, and “deep learning”. Conclusions: EEG constitutes the most significant input in brain-computer interfaces (BCI) and can be successfully used in the neurorehabilitation of patients with stroke, amyotrophic lateral sclerosis, and traumatic brain and spinal injury. EEG-based BCI facilitates training, communication, and control of wheelchair and exoskeletons. However, research is limited to specific scientific groups from developed countries. Evidence is expected to change with the broader availability of BCI and improvement in EEG filtering algorithms.

Mirror Therapy (MT) and Cognitive Therapeutic Exercise (CTE) are two neurorehabilitation techniques based on neuroplasticity and designed to enhance the functionality of the upper limb. Therefore, the aim is to assess the effectiveness of the combination of CTE and MT with task-oriented training (TOT) on fine and gross motor skills of the affected hand, as well as the functionality of the affected upper limb, autonomy, independence, and quality of life (QoL) in patients with acute stroke. This longitudinal and multicenter study involved a sample of 120 participants selected randomly and consecutively. Three groups were formed, including a control group (CG) and two treatment groups, one with MT and the other with CTE. The functionality of the upper limb, fine and gross motor skills, the quantity and quality of use of the affected upper limb, autonomy, and QoL were evaluated using various scales validated in the Spanish population at the baseline, after 20 treatment sessions, and at three months of follow-up. ANCOVA analysis was conducted, revealing statistically significant differences between assessments in the CG compared to the experimental groups (GEs), indicating a notable improvement in overall functionality, fine and gross motor skills, autonomy, and QoL in the latter. However, there were no significant differences between the GEs. Therefore, the application of either of these experimental combinations is crucial for the motor recovery, functionality, and improvement of the quality of life of individuals who have suffered a stroke.

CT scans are currently the most common imaging modality used for suspected stroke patients due to their short acquisition time and wide availability. However, MRI offers superior tissue contrast and image quality. In this study, eight deep learning models are developed, trained, and tested using a dataset of 181 CT/MR pairs from stroke patients. The resultant synthetic MRIs generated by these models are compared through a variety of qualitative and quantitative methods. The synthetic MRIs generated by a 3D UNet model consistently demonstrated superior performance across all methods of evaluation. Overall, the generation of synthetic MRIs from CT scans using the methods described in this paper produces realistic MRIs that can guide the registration of CT scans to MRI atlases. The synthetic MRIs enable the segmentation of white matter, gray matter, and cerebrospinal fluid using algorithms designed for MRIs, exhibiting a high degree of similarity to true MRIs.

Background: The increased vascular risk associated to Varicella- Zoster Virus (VZV) reactivation is extensively established in the general population. This retrospective cohort study investigates whether this observation holds true for People Living With HIV (PLWH), a group already con-fronting heightened cardiovascular risk. Methods: Among PLWH who initiated antiretroviral therapy (ART) at our center and have been under our care for > 24 months since January 1st, 2005, individuals with a history of Herpes Zoster (HZ) were identified and compared their features with those of PLWH with no history of HZ. The prevalence of ischemic events (Deep Venous Thrombosis, Stroke, Acute Myocardial Infarction) was calculated and compared using Chi Square. Odds Ratios (O.R.) with 95% Confidence Intervals (C.I.) for ischemic events following HZ were evaluated through univariate and multivariate logistic regression. Results: Overall, 45/581 PLWH reported HZ. Ischemic events followed HZ significantly more often than the other group (13% vs. 5%, p=0.01). Both positive serology for VZV and HZ correlated with increased ischemic risk (O.R. 4.01, 95% C.I. 1.38-11.6, p=0.01 and O.R. 3.14, 95% C.I. 1.12-7.68, p=0.02, respectively), though pre-existing heart disease demonstrated stronger predictive value in multivariate analysis(O.R. 8.68, 95% C.I. 2.49-29.50, p=0.001). Conclusions: VZV potentially exacerbates vascular risk for PLWH, particularly in the presence of other predisposing factors. Further research is needed to confirm our data.

Repetitive transcranial magnetic stimulation (rTMS) with intensive occupational therapy improves upper limb motor paralysis and activities of daily living after stroke; however, amount of improvement according to paralysis severity remains unverified. Target activities for daily living using patients’ upper limb functions can be established by predicting the amount of change after treatment for each severity level of upper limb motor paralysis and further aid practice planning. This study estimated post-treatment score changes for each severity level of motor paralysis (no, poor, limited, notable, and full) stratified according to Action Research Arm Test (ARAT) scores before combined rTMS and intensive occupational therapy. Severity of motor paralysis was the fixed factor for analysis of covariance, delta (post-pre) of the scores was the dependent variable. Ordinal logistic regression analysis was used to compare changes in ARAT subscores in patients, divided according to paralysis severity before treatment. A multicenter retrospective cohort dataset analyzed 907 patients with stroke hemiplegia. Largest treatment-related changes in scores were observed in the Limited recovery group for upper limb motor paralysis and Full recovery group for quality-of-life activities using paralyzed upper limb. These results will help predict treatment effects and determine exercises and goal movements for occupational therapy after rTMS.

Neurodegenerative diseases encompass a broad spectrum of profoundly disabling disorders that impact millions of individuals globally. While their underlying causes and pathophysiol-ogy display considerable diversity and remain incompletely understood, a mounting body of evidence indicates that the disruption of blood-brain barrier (BBB) permeability, resulting in brain damage and neuroinflammation, constitutes a shared characteristic among them. Con-sequently, targeting the BBB has emerged as an innovative therapeutic strategy for address-ing neurological diseases. Within this review, we not only explore the neuroprotective, neu-rotrophic, and immunomodulatory benefits of mesenchymal stem cells (MSCs) in combating neurodegeneration but also delve into their recent role in modulating the BBB. We will delve into the cellular and molecular mechanisms through which MSC treatment impacts primary age-related neurological disorders like Alzheimer’s disease, Parkinson’s disease, and stroke as well as immune-mediated conditions such as multiple sclerosis. Our focus will center on how MSCs participate in the modulation of cell transporters, matrix remodeling, stabilization of cell-junction components, and restoration of BBB network integrity in these pathological con-texts.

Physical exercise is the greatest stress on the cardiovascular system, not only in humans but also in all vertebrates. Consequently, the cardiovascular response cannot be thought of as having only one "anthropocentric" interpretation. The modulation of cardiac output (Q) in response to exercise in the five major groups of vertebrates exhibits considerable variability. Moreover, the response of the heart rate (HR) and the stroke volume (SV), the fundamental factors that cause the rise in Q, is also highly variable. The difference in the range of HR is difficult to determine in many vertebrates, both at rest and at maximal effort. Additionally, the increase in SV varies among vertebrates. For example, while rainbow trout and leopards increase their SV by increasing end diastolic volume (EDV), humans do so at the expense of both increasing EDV and reducing end systolic volume (ESV). The variation in arterial pressure that arises during exercise varies notably among vertebrates, such as amphibians, whose blood pressure values do not increase as significantly as in mammals. Such differences in cardiovascular response among vertebrates may be linked to their habitat or living environment. This review aims to analyze the cardiovascular response of vertebrates to physical exercise as the most common stressor.

Not in the history of transmissible illnesses has there been an infection as strongly associated with acute cerebrovascular disease as the novel human coronavirus, SARS-CoV-2. While the risk of stroke has known associations with other viral infections, such as influenza and human immunodeficiency virus, the risk of ischemic and hemorrhagic stroke related to SARS-CoV-2 is unprecedented. Furthermore, the coronavirus disease 2019 (COVID-19) pandemic has so profoundly impacted psychosocial behaviors and modern medical care that we have witnessed shifts in epidemiology and have adapted our treatment practices to reduce transmission, address delayed diagnoses, and mitigate gaps in health care. In this narrative review, we summarize the history and impact of the COVID-19 pandemic on cerebrovascular disease, and lessons learned regarding the management of patients as we endure this period of human history.

Radiologists refer to any area of cerebral parenchymal loss with or without surrounding gliosis as encephalomalacia. This archaic phrase, which literally translates to "softening of the brain" due to liquefactive necrosis, was coined by pathologists to describe the macroscopic appearance of the brain following a variety of traumas, such as cerebral infarction. The final outcome of brain parenchymal liquefactive necrosis after insult, which typically happens after cerebral ischemia, cerebral infection, hemorrhage, traumatic brain damage, surgery, or other insults. Gliosis, or the growth of glial cells in reaction to injury, is frequently seen around it. The location, size, and number of the lesions as well as the existence of other issues like seizures, hydrocephalus, or infection affect the symptoms and prognosis of encephalomalacia. While some people might not have any symptoms, others might have neurological abnormalities such hemiparesis, aphasia, cognitive decline, or behavioral changes. Depending on the underlying reason and the severity of the problem, treatment options may include medication, surgery, or rehabilitation. This is a case of a young male who reported for rehabilitation his left upper limb weakness, upon investigations Encephalomalacia was diagnosed.

The present review aimed to identify through what means neurologic injury can predispose individuals to Post-Traumatic Stress Disorder (PTSD). In recent years, comprehensive studies have helped to clarify which structures in the central nervous system (CNS) that, when damaged, lead to distinct PTSD symptoms–namely dissociative reactions or flashbacks. Our review narrowed its focus to three common neurologic injuries including traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and stroke. Beyond discussing the potential mechanisms by which neurotrauma may lead to PTSD, we summarized our current understanding of the pathophysiology of the disorder and discussed predicted associations between the limbic system and PTSD. In particular, the role of noradrenergic neuromodulatory signaling on the HPA axis as it pertains to fear memory recall needs to be further explored to better understand its effects on limbic structures in PTSD patients. This paper also described how damage to the CNS can alter the function of the limbic system and result in characteristic symptoms of PTSD like intrusive memories and acute psychological distress. Further, our review intended to draw attention to a lack of PTSD prognosis in TBI, SAH, and stroke patients who could benefit from early treatment. PTSD symptoms often compound with pre-existing issues further deteriorating health outcomes for these patients. It is ultimately our goal to clarify the relationship between neurotrauma and PTSD such that earlier diagnoses and appropriate treatment are observed in clinic.

Traditional end-effector robots for arm rehabilitation are usually attached a­t the hand, primarily focusing on coordinated multi-joint training. Therapy at an individual joint level of the arm for severely impaired stroke survivors is not always possible with existing end-effector robots. The Arm Rehabilitation Robot (AREBO)—an end-effector robot—was designed to provide both single and multi-joint assisted training while retaining the advantages of traditional end-effector robots, such as ease of use and cost-effectiveness (compared to exoskeletons). This work presents the design, optimization, and characterization of AREBO for training single-joint movements of the arm. The AREBO has three actuated and three unactuated degrees of freedom, allowing it to apply forces in any arbitrary direction at its endpoint and self-align to arbitrary orientations within its workspace. The AREBO’s link lengths were optimized to maximize its workspace and manipulability. The AREBO provides single-joint training in both unassisted and adaptive weight support modes using a human arm model to estimate the human arm's kinematics and dynamics without using additional sensors. The characterization of the robot’s controller and the algorithm for estimating the human arm parameters were performed using a two degrees of freedom mechatronic model of the human shoulder joint. The results demonstrate that: (a) the movements of the human arm can be estimated using a model of the human arm and robot’s kinematics, (b) the AREBO has similar transparency to that of existing arm therapy robots in the literature, and (c) the adaptive weight support mode control can adapt to different levels of impairment in the arm. This work demonstrates how an appropriately designed end-effector robot can be used for single-joint training, which can be easily extended to multi-joint training. Future work will focus on the evaluation of the system on patients with any neurological condition requiring arm training.

The aim of this study was to measure one-year total cost of stroke and to investigate the value of stroke care, defined as cost per QALY. The study population included 892 patients with first ever acute stroke, hemorrhagic and ischemic, (ICD-10 codes: I61, I63 and I64) admitted within 48 hours of symptoms onset to nine public hospitals located in six cities. We conducted a bottom-up cost analysis from the societal point of view. All cost components including direct medical costs, productivity losses due to morbidity and mortality and informal care costs were considered. We used an annual time horizon, including all costs for 2021 irrespective of the time of disease onset. The average cost (direct and indirect) was extrapolated in order to estimate the national annual burden associated with stroke. We estimated the total cost of stroke in Greece at €343.1 mil a year in 2021, (€10,722/patient or €23,308 per QALY). Out of €343.1 mil., 53.3% (€182.9 mil) consisted direct healthcare cost representing 1.1% of current health expenditure in 2021. Overall, productivity losses were calculated at €160.2 mil. The mean productivity losses were estimated to 116 work days with 55.1 days lost due to premature retirement and absenteeism from work, 18.5 days lost due to mortality and 42.4 days lost due to informal caregiving by family members.This study highlights the burden of stroke and underlines the need for stakeholders and policy makers to re-organize stroke care and promote interventions that have been proved as cost-effective

Informal caregivers are essential in supporting stroke survivors' recovery, but it is unclear whether community interventions can promote healthy eating behaviors and social participation among stroke survivors and their caregivers. The Train-Your-Brain (TYB) program's impact on adherence to national dietary guidelines and social participation among informal caregivers and stroke survivors were assessed in a quasi-experimental study. The TYB program had nine sessions, with one focusing on healthy lifestyle. Participants were prompted to discuss the topics covered, leading to social participation. Dietary habits were assessed using fruits and vegetables consumption questions, while social participation was measured using the Social Impact Measurement Framework. Mann-Whitney U-test and Wilcoxon Signed Rank Test were utilized to analyze the data. Eighteen informal caregivers and 27 stroke survivors participated in the program. Results showed a significant increase in fruit and vegetable intake and social participation in informal caregivers after the program, but there were no significant changes in stroke survivors. Informal caregivers play a crucial role in stroke survivors' lifestyle habits and in encouraging social connections with other stroke survivors. Thus, healthcare professionals should prioritize caregiver support and education to facilitate long-term dietary and social changes that can positively impact stroke survivor's recovery and quality of life.

A large proportion of chronic stroke survivors still struggle with upper limb (UL) problems in daily activities. We investigated clinical outcomes and assessed the quality of movement before and after a 5-hour error-enhancement training. The pilot study had a pre-post intervention design, recruiting 22 patients in the chronic phase post-stroke with UL motor impairments. Patients received 1-hour robot treatment for five days. Patients were assessed at baseline and after training, collecting (1) clinical (UL Fugl-Meyer assessment (FMA-UE)), action research arm test (ARAT), motor assessment scale UL and tone), (2) patient-reported (hand subscale of the stroke impact scale, motor activity log (MAL), visual analogue scale of pain and tone) and (3) kinematic (KINARM, BKIN Technologies Ltd., Canada) outcome measures. Our analysis revealed significant improvements (median im-provement (Q1-Q3); p<0.05) in (1) FMA-UE (1.0 (0.8–3.0), p<0.001) and ARAT (2 (0.8–2.0), p<0.001); (2) MAL amount of use (0.1 (0.0–0.3), p<0.001) and MAL quality of use (0.1 (0.1–0.5), p<0.001); (3) KINARM-evaluated position sense ((-0.45 (-0.81–0.09), p=0.030) after training. These findings provide insight into kinematic, clinical, and self-reported improvements in UL functioning after five hours of error-enhancement UL training.