ARTICLE | doi:10.20944/preprints201904.0212.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: stroke; post-stroke dementia; anaemia
Online: 19 April 2019 (09:41:13 CEST)
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.
ARTICLE | doi:10.20944/preprints202107.0490.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: miRNAs; stroke; acute ischemic stroke; biomarkers; meta-analysis.
Online: 21 July 2021 (11:57:02 CEST)
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.
Subject: Social Sciences, Psychology Keywords: mindfulness; mindfulness-based stress reduction; mindfulness-based stroke recovery; stroke recovery; social support for stroke survivors; medical education; stroke rehabilitation
Online: 12 September 2020 (11:29:22 CEST)
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.
ARTICLE | doi:10.20944/preprints202306.1743.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: essential thrombosis; ischemic stroke; JAK2; recurrent stroke; cytoreductive therapy
Online: 26 June 2023 (05:18:19 CEST)
Objectives: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by elevated platelet counts and an increased risk of thrombotic events, including ischemic strokes. Methods: We conducted a retrospective analysis of data from consecutive ischemic stroke patients with ET between March 2014 and February 2023. Results: This case series describes the clinical presentation, radiological features, and management of five patients with ET-associated ischemic strokes, all harboring the JAK2 mutation. The diverse radiological findings suggest that both large and small vessel diseases may be influenced by the prothrombotic state induced by ET. A significant elevation in platelet count was observed to correlate with the emergence of new acute infarctions in some cases. Conclusions: The study highlights combined use of antiplatelet and cytoreductive therapy in preventing secondary stroke events in patients with ET and JAK2 mutations. The heterogeneity of stroke patterns in this population necessitates a comprehensive understanding of the underlying pathophysiological mechanisms and tailored therapeutic approaches.
ARTICLE | doi:10.20944/preprints201808.0455.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Anaemia; Stroke; Dementia; Risk; Vascular Dementia; Post-stroke dementia
Online: 27 August 2018 (11:11:59 CEST)
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.
CASE REPORT | doi:10.20944/preprints202311.0292.v1
Online: 6 November 2023 (08:05:25 CET)
Granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis, is a rare form of necrotizing granulomatous inflammation that predominantly affects medium and small size vessels. Generally respiratory tracts and kidneys are the most affected organs. Neurological manifestations of GPA usually involve the peripheral nervous system causing mononeuritis multiplex or and cranial nerve palsies. Central nervous system (CNS) involvement is rare and characterized by cerebral vasculitis, meningeal inflammation, or mass lesions. The CNS involvement is often linked to Ear Nose Throat (ENT) system disease. In this report, we present two cases of patients diagnosed with GPA who exhibit CNS involvement as first symptom. In the first one with an ischemic stroke while in the second with an atypical headache. In the first patient, a positive medical history indicating involvement of the Ear, Nose, and Throat (ENT) facilitated a precise diagnosis through the prompt execution of autoimmune screening. This, in turn, enabled a timely commencement of treatment, resulting in neurological improvement. In the second case, the significance of ENT involvement was initially overlooked in the context of pathological definition, leading to a substantial delay in diagnosis and an ultimately grim prognosis for the patient. The ENT involvement could be an easy marker to suspect GPA in patient with atypical CNS presentation and could help to make a prompt diagnosis.
ARTICLE | doi:10.20944/preprints202007.0444.v1
Online: 19 July 2020 (20:57:58 CEST)
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.
REVIEW | doi:10.20944/preprints202102.0291.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: stroke; neutrophil lymphocyte ratio; Systemic Immune Inflmmatory Indea; sustainable stroke care
Online: 11 February 2021 (19:01:45 CET)
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.
ARTICLE | doi:10.20944/preprints201906.0048.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: Ambulation, Ischemic stroke, pre-stroke depression, recombinant tissue plasminogen activator (rtPA)
Online: 6 June 2019 (10:37:13 CEST)
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.
REVIEW | doi:10.20944/preprints202311.0470.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: social support; depression; stroke
Online: 7 November 2023 (13:25:24 CET)
Research has shown a protective association between social support and depression, depression among stroke patients, and health impacts of depression. Yet not much is known on the effect of social support on depression among stroke patients. This review aims to summarize the current research examining the association between social support and depression among stroke patients. A literature search was performed in PubMed to find original peer-reviewed journal articles from 2016 to Mar. 12, 2023 that examined the association between social support and depression among stroke patients. The search terms were depression and "social support" and stroke, which lead to 172 articles. After abstract review, seven observational studies that studied the target association among stroke patients were selected. One additional study was found using PsycINFO as a complementary source with the same search strategy and criteria. Overall, a negative association was found between social support and depression among stroke patients in seven studies, with more social support leading to lower rates of depression post-stroke. One study found that social support was positively related with depression, but the result was nonsignificant. Overall, the results of recent studies suggest that social support is negatively associated with depression among stroke patients. In most studies, this association was statistically significant. The findings suggest the importance of improving social support perceived by stroke patients in the prevention of depression after the occurrence of stroke.
ARTICLE | doi:10.20944/preprints202310.1950.v1
Subject: Public Health And Healthcare, Physical Therapy, Sports Therapy And Rehabilitation Keywords: stroke, rehabilitation, sitting position
Online: 30 October 2023 (14:56:59 CET)
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.
REVIEW | doi:10.20944/preprints202104.0476.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Dysphagia, Nursing, Screening, Stroke
Online: 19 April 2021 (12:23:23 CEST)
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
REVIEW | doi:10.20944/preprints202104.0197.v1
Online: 7 April 2021 (11:45:33 CEST)
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
ARTICLE | doi:10.20944/preprints202303.0264.v1
Subject: Social Sciences, Behavior Sciences Keywords: post-stroke; community intervention; stroke survivors; caregivers; diet; fruits; vegetables; social participation
Online: 15 March 2023 (01:47:14 CET)
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.
REVIEW | doi:10.20944/preprints202207.0412.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: stroke; hypereosinophilia; hypereosinophilic syndrome (HES); brain MRI; embolic pattern; border zone stroke
Online: 27 July 2022 (05:30:13 CEST)
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.
ARTICLE | doi:10.20944/preprints201908.0211.v2
Subject: Public Health And Healthcare, Physical Therapy, Sports Therapy And Rehabilitation Keywords: Rehabilitation, Stroke, Long-term care, Quality of life, Post-stroke checklist, Unmet needs
Online: 26 August 2019 (12:21:22 CEST)
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.
ARTICLE | doi:10.20944/preprints202310.1319.v2
Subject: Public Health And Healthcare, Physical Therapy, Sports Therapy And Rehabilitation Keywords: stroke; physiotherapy; goals; hope; training
Online: 20 October 2023 (12:11:26 CEST)
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.
INTERESTING IMAGES | doi:10.20944/preprints202309.0612.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Encephalomalacia; gliosis; cerebral softening; stroke
Online: 11 September 2023 (09:37:33 CEST)
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.
REVIEW | doi:10.20944/preprints202109.0446.v2
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: ischemic stroke; safety; cerebrolysin; neurorehabilitation
Online: 15 November 2021 (10:46:02 CET)
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.
REVIEW | doi:10.20944/preprints202108.0448.v2
Subject: Medicine And Pharmacology, Hematology Keywords: stroke; cellular senescence; coagulation; adhesion
Online: 14 October 2021 (15:21:58 CEST)
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.
ARTICLE | doi:10.20944/preprints201905.0153.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: vitamin D; stroke; meta-analysis
Online: 13 May 2019 (10:16:48 CEST)
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.
CONCEPT PAPER | doi:10.20944/preprints202102.0328.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Systems biology, stroke, neuroinflmmation, NLR,systemic immune inflmmation index, Post Stroke Neurological Syndrome (PSNS)
Online: 16 February 2021 (13:38:58 CET)
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).
REVIEW | doi:10.20944/preprints202304.0094.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: stroke; ischemia; neuroprotection; SUMOylation; experimental therapeutics
Online: 6 April 2023 (12:21:33 CEST)
Small, Ubiquitin-like Modifier (SUMO) is a post-translational modifier with a profound influence on several key biological processes including the mammalian stress response. Of particular interest is its neuroprotective effects, first recognized in the 13-lined ground squirrel (Ictidomys tridecemlineatus), in the context of hibernation torpor. Although the full scope of the SUMO pathway is yet to be elucidated, observations of its importance in managing neuronal responses to ischemia, maintaining ion gradients, and preconditioning of neural stem cells, make it a promising therapeutic target for acute cerebral ischemia. Recent advances in high-throughput screening have enabled the identification of small molecules that can upregulate SUMOylation, some of which have been validated in pertinent preclinical models of cerebral ischemia. Accordingly, the present review aims to summarize current knowledge and highlight the translational potential of the SUMOylation pathway in brain ischemia.
REVIEW | doi:10.20944/preprints202207.0374.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: probiotic; stroke; gut microbiome; meta-analysis
Online: 25 July 2022 (11:37:22 CEST)
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.
REVIEW | doi:10.20944/preprints202207.0154.v1
Subject: Social Sciences, Behavior Sciences Keywords: post-stroke aphasia; pharmacotherapy; cholinergic treatment
Online: 11 July 2022 (08:58:05 CEST)
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.
REVIEW | doi:10.20944/preprints202008.0094.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Ischemic Stroke; Reperfusion; Neuroprotection; Nerinetide; Kv2.1
Online: 4 August 2020 (11:28:48 CEST)
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.
Subject: Biology And Life Sciences, Behavioral Sciences Keywords: Elderly; epilepsy; stroke; Parkinson’s disease; fall
Online: 7 February 2019 (11:26:29 CET)
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.
ARTICLE | doi:10.20944/preprints201711.0173.v1
Subject: Public Health And Healthcare, Nursing Keywords: instruction; perceived threat; caregivers; stroke; dependency
Online: 27 November 2017 (07:56:30 CET)
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.
REVIEW | doi:10.20944/preprints201701.0027.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: iPad; tablet computers; Stroke; neuro-rehabilitation
Online: 5 January 2017 (09:56:53 CET)
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.
ARTICLE | doi:10.20944/preprints201610.0083.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: stroke; antioxidant; co-drug; animal model
Online: 20 October 2016 (08:46:38 CEST)
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.
ARTICLE | doi:10.20944/preprints202311.0625.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: ischemic stroke; MRI; morphometry; post-stroke cognitive impairment, post-stroke depressive disorder; cortisol; α-amylase; interleukin-6; multiple hit hypothesis; hypothalamic-pituitary-adrenal axis; sympathoadrenal system
Online: 9 November 2023 (10:06:30 CET)
Post-stroke depressive disorders (PSD) and post-stroke cognitive impairments (PCI) are frequent consequences of ischemic stroke (IS). The study was focused on exploring possible associations between relative volumes of cortical and limbic brain structures during the acute period of IS, and changes in biochemical indices of hypothalamic-pituitary-adrenal, sympathoadrenal medullary and inflammatory systems, with the development of PSD or PCI after mild or moderate IS. Patients developing PSD later on had significantly smaller relative volumes of the hippocampus, entorhinal cortex, and temporal pole versus patients without depressive symptoms. PCI development was associated with significantly smaller volumes of temporal pole and supramarginal gyrus versus patients without cognitive changes. Multiple logistic regression analysis showed higher likelihood of developing PSD in patients with smaller temporal pole volume (β0=10.9; β=-4.27; p=0.04) and increased salivary α-amylase activity (β0=-3.55; β=2.68e-05; p=0.02,). PCI likelihood was higher in patients with smaller supramarginal gyrus volume (β0=3.41; β=-0.99; p=0.047), smaller temporal pole volume (β0=3.41; β=-3.12; p=0. 06), and increased hair cortisol concentration at admission (index of accumulated stress load within a month before IS; β0=3.41; β=-0.05; p=0.08). The data support the hypothesis suggesting predisposition to PSD and PCI and multi hit scenarios of their pathogenesis with IS providing a final hit.
REVIEW | doi:10.20944/preprints202311.0571.v1
Subject: Public Health And Healthcare, Physical Therapy, Sports Therapy And Rehabilitation Keywords: post‐stroke; dependence variable; telerehabilitation; review; telecare
Online: 8 November 2023 (16:14:02 CET)
Introduction: Outcome measures using telerehabilitation (TR) in the context of post-stroke rehabilitation is an area of emerging research. The current review assesses the literature related to TR for patients requiring post-stroke rehabilitation. The purpose of this study additionally is to survey the outcome measures used in TR studies and to define which parts of the International Organization of Functioning are measured in trials. Methods: TR studies were searched in Cochrane Central Register of Controlled Trials, PubMed, Embase, Scopus, Google Scholar, and Web of Science from 2016 to June 2023. Two reviewers individually assessed the full text. Disagreements about inclusion or exclusion were determined by consensus or by checking with a third reviewer. Results: A total of 24 studies were included in the current review. The results were synthesized and reported considering the implications of the results within clinical practice, areas of investigation, and strategic implementation. Conclusions: The current scoping review recognized a wide range of outcome measures used in TR studies and helped elucidate gaps in the current use of outcome measures in the literature. The scoping review also informs researchers and end users (i.e. clinicians and policymakers) regarding the most suitable outcome measures for TR.
ARTICLE | doi:10.20944/preprints202311.0040.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: ischemic stroke; quality of care; racial disparity
Online: 1 November 2023 (10:24:31 CET)
Introduction: This analysis is conducted as a part of a quality improvement project aiming at identifying racial disparity in inpatient stroke quality of care. Methods: Get With The Guidelines (GWTG) database was used to identify all patients discharged with any stroke diagnosis between January and December 2021. Additional chart review was conducted to ensure the accuracy of racial/ethnic categorization. The sample was dichotomized to White vs non-White groups and compared with univariate analysis. Results: The study sample comprised 1,408 encounters (1,347 patients). Mean age 71±15 years, 51% women, 82% White patients, 15% non-White patients, 72% acute ischemic stroke (AIS); 15% transient ischemic attack (TIA), 9% intracerebral hemorrhage (ICH), 3% subarachnoid hemorrhage (SAH), and 1% stroke not otherwise specified. Non-White patients were younger, had fewer concomitant diagnoses, lower proportion of TIA and higher proportion of ICH (p=0.004). In AIS cohort, compared to White patients, non-White patients had less frequent ambulance (p=0.009), arrived to the hospital later than White patients (7.7 hours longer ; p<0.001), had more severe stroke, and had less frequent IV thrombolysis utilization (7% vs 13%; p=0.042). Similarly in the TIA cohort, non-White patients’ utilization of EMS was lower than White patients and their hospital arrival was delayed. In the ICH cohort, non-White patients were younger, had lower frequency of atrial fibrillation, and a non-significant trend towards higher disease severity. The SAH cohort had only 8 non-White patients, 6 of which were transferred to higher level of care hospital within a few hours of arrival, therefore. Importantly, the hospital-based quality metrics such as door-to-CT time, door-to-needle time, and the Joint Commission stroke quality metrics were similar between the two groups. Conclusion: There is a racial disparity in the pre-hospital phase of the stroke chain of survival of non-White patients impacting the IV thrombolysis utilization. The younger age and worse lipid profile and hemoglobin A1C of non-White patients suggest the need for better preventative care starting at young age.
CASE REPORT | doi:10.20944/preprints202309.1154.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: pediatric stroke; basilar artery occlusion; mechanical thrombectomy
Online: 18 September 2023 (13:36:23 CEST)
Studies have shown the benefits of endovascular treatment (EVT) in adult stroke cases, but its application in pediatric stroke remains controversial. Despite evidence of improved outcomes in adults, there are no established recommendations for EVT in children. Conducting individual case reports and case series is vital to understanding its potential advantages and disadvantages in this context. This case report presents a 9-year-old boy who experienced basilar artery occlusion leading to a stroke and was effectively treated with mechanical thrombectomy.
ARTICLE | doi:10.20944/preprints202308.2193.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: inflammation; stroke; atheromatosis; biomarker; interleukin 1 beta
Online: 31 August 2023 (12:47:13 CEST)
Background and Objectives: Stroke is a main leading cause for mortality and morbidity worldwide. Treat-ment of this pathology is still under development and its risk factors remain the main target to be reached. Therefore, we aim to determine the role of interleukin 1 beta in atheromatosis, as risk factor for stroke and the reole of this biomarker in stroke prognosis. Materials and Methods: The study conducted enrolled 56 patients diagnosed with ischemic stroke in the anterior (AVT) and posterior vascular territory (PVT). All patients had venous blood collected at admission and 7 days after the onset of the cerebral ischemia in order to determine plasma concentration for interleukin 1 beta. At the same time an extracranial carotid ultrasound was performed. Results: Interleukin 1 beta collected at admission was positively correlated with NIHSS at admission (Pearson index 0,424) and both measurements were corelated with carotid stenosis (Spearmen correlation index 0,529, respectively 0,653). Conclusion: Interleukin 1 beta could be a reliable biomarker for stroke prognosis and carotid atheromatosis development.
ARTICLE | doi:10.20944/preprints202307.1626.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: Proton pump inhibitors; Clopidogrel; Stroke; Myocardial infarction
Online: 25 July 2023 (07:26:31 CEST)
Background/Aims: Conflicting results have been reported regarding the interaction between proton pump inhibitors (PPIs) and clopidogrel. We investigated whether concomitant PPI use influenced the risk of recurrence in patients with stroke and myocardial infarction (MI). Methods: This study used two databases for different designs, the Korean National Health Insurance Service (NHIS) database for a self-controlled case series design, and the national sample cohort of the NHIS database converted to the Observational Medical Outcomes Partnership-Common Data Model version for a cohort study. Results: In the PPI co-prescription group, recurrent hospitalization with stroke occurred in 17.6% of the 8,201 patients with history of stroke, and recurrent MI occurred in 17.1% of the 1,216 patients with history of MI during 1 year. According to the self-controlled case series, the overall relative risk (RR) of recurrent stroke was 2.09 [95% confidence interval (CI); 1.83-2.38], and the RR showed an increasing trend with PPI duration. In the cohort study, there was a higher incidence of recurrent stroke in the PPI co-prescription group [Hazard ratio (HR): 1.34, 95% CI: 1.01-1.76, P=0.04]. The overall RR of recurrent MI was 1.47 (95% CI; 1.02-2.11) in the self-controlled case series; however, there was no statistically significant difference in recurrent MI in the cohort study (HR:1.42, 95% CI:0.79-2.49, P=0.23). The impact of individual PPIs on stroke and MI showed different patterns. Conclusions: PPI co-prescription with clopidogrel was associated with recurrent stroke; however, its association with recurrent MI remains inconclusive. The influence of individual PPIs should be clarified in the future.
ARTICLE | doi:10.20944/preprints202307.1286.v1
Subject: Public Health And Healthcare, Physical Therapy, Sports Therapy And Rehabilitation Keywords: stroke rehabilitation; home therapy; telerehabilitation; rehabilitation robotics
Online: 19 July 2023 (04:52:24 CEST)
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.
ARTICLE | doi:10.20944/preprints202307.1054.v1
Subject: Medicine And Pharmacology, Pharmacy Keywords: reconstituted lipid nanoparticles; selective homing; ischemic stroke
Online: 17 July 2023 (10:46:20 CEST)
Lipid nanoparticles (LNPs) are promising carriers for constructing drug delivery systems (DDSs) in disease treatments. Previous studies have suggested that lipid composition and biophysical properties of LNPs can significantly impact their interaction with cells and tissues, allowing for the development of suitable LNPs for precise drug delivery. Our previous study proposed the concept and facile preparation of reconstituted lipid nanoparticles (rLNPs), which not only have the advantages of traditional LNPs but also contain the lipids of mother cell/tissue. In this study, we have found that brain-derived rLNPs (B-rLNPs) can have much better accumulation to the ischemic area of the ischemic stroke (IS) model than liver-derived rLNPs (L-rLNPs). This homing effect hopefully makes rLNPs a useful tool for developing highly accessible devices with homologous targeting ability for precise drug delivery.
ARTICLE | doi:10.20944/preprints202307.0116.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: Stroke; Ultrasonography; Postural balance, Multifidus; Cervical muscle.
Online: 6 July 2023 (13:23:24 CEST)
Background: The aim of this study was to examine cervical multifidus muscle morphology and its impact on postural balance in patients with post-stroke. Methods: This is a pilot study. A convenience sample of 24 volunteers of 67 ±8.5 years (12 with hemiparesis due to post-stroke, 12 healthy) was recruited for this study. The outcomes measured were the thickness of the multifidus muscle using ultrasonography, Modified Functional Reach Test (MFRT), Timed Up and Go (TUG) test and Berg Balance scale (BBS). Results: No significant differences in the ultrasound values between stroke patients' paretic and non-paretic sides were found. Similarly, there were no significant differences between the non-paretic side of stroke patients and the non-paretic side of the control group, (all, p>0.05). Additionally, no significant correlations between the ultrasonographic variables of the multifidus muscles and the main outcome measures were identified. Conclusions: In conclusion, our study did not find significant differences in cervical multifidus muscle morphology between healthy individuals and post-stroke patients in relation to postural balance.
BRIEF REPORT | doi:10.20944/preprints202110.0398.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: stroke; thrombolysis; Culturally linguistically diverse communities (CALD)
Online: 27 October 2021 (10:56:23 CEST)
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.
COMMUNICATION | doi:10.20944/preprints202108.0302.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: stroke; liposome; cerebrovascular disease; oxidative stress; dementia
Online: 13 August 2021 (15:37:59 CEST)
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.
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Stroke; Qualitative; Narrative; Master Plot; Experience; Perception
Online: 30 July 2021 (15:10:28 CEST)
(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.
ARTICLE | doi:10.20944/preprints202006.0338.v1
Subject: Medicine And Pharmacology, Other Keywords: Gait; Stroke; Cerebellum; Transcranial Direct Current Stimulation
Online: 28 June 2020 (10:16:17 CEST)
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.
REVIEW | doi:10.20944/preprints201908.0082.v1
Subject: Medicine And Pharmacology, Dietetics And Nutrition Keywords: overview; meta-analyses; stroke; nutrition; geographical areas
Online: 6 August 2019 (16:18:23 CEST)
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.
ARTICLE | doi:10.20944/preprints202209.0417.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Recreational substance abuse; drug abuse; marijuana; amphetamine; acute ischemic stroke; risk factors; young adult; NIS; Stroke; Sudden Cardiac Death
Online: 27 September 2022 (09:41:00 CEST)
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.
ARTICLE | doi:10.20944/preprints202310.1716.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: stroke; aging; mitochondrial biogenesis; beta-2-adrenergic activation
Online: 26 October 2023 (12:16:31 CEST)
Following ischemic stroke, the degradation of myelin and other cellular membranes surpasses the lipid-processing capabilities of resident microglia and infiltrating macrophages. This imbalance leads to foam cell formation in the infarct and areas of secondary neurodegeneration, instigating sustained inflammation and furthering neurological damage. Given that mitochondria are the primary sites of fatty acid metabolism, augmenting mitochondrial biogenesis (MB) may enhance lipid processing, curtailing foam cell formation and post-stroke chronic inflammation. Previous studies have shown that the pharmacological activation of the β2-adrenergic receptor (β2-AR) stimulates MB. Consequently, our study sought to discern the effects of intensified β2-AR signal-ing on MB, the processing of brain lipid debris, and neurological outcome using a mouse stroke model. To achieve this goal, aged mice were treated with formoterol, a long-acting β2-AR ago-nist, daily for two and eight weeks following stroke. Formoterol increased MB in the infarct re-gion, modified fatty acid metabolism, and reduced foam cell formation. However, it did not re-duce markers of post-stroke neurodegeneration or improve recovery. Our findings suggest that boosting MB in myeloid cells is one component of a therapeutic avenue for improving brain lipid debris processing after stroke.
ARTICLE | doi:10.20944/preprints202310.1351.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: Stroke; gut microbiota; butyric acid; microglia; astrocytes; NLRP3
Online: 20 October 2023 (11:53:16 CEST)
Ischemic stroke (IS) is a group of vascular disease concomitant with high morbidity and mortality. Berberine is a bioactive substance and it has known to improve stroke, but the mechanism is yet to be proven. Mice were fed with BBR for 14 days. Then, mice were made into MCAO/R models. Neurological score, infarct volume, neuronal damage and markers associated with inflammation were detected. We tested the changes of intestinal flora in model mice after BBR administration by 16SrRNA sequencing. Chromatography-mass spectrometry was used to detect butyrate chemically. Tissue immunofluorescence was used to detect the changes of microglia and astroglia in mice brain. Our findings suggest that berberine improves stroke outcomes by modulating gut microbiota. Specifically, after MCAO/R mice were given berberine, beneficial bacteria producing butyric acid increased significantly, and the mice also had significantly higher levels of butyric acid. Administration of butyric acid and an inhibitor of butyric acid synthesis, heptyl-coA, showed that butyric acid improved stroke outcomes in model mice. In addition, butyric acid could inhibit the activation of microglia and astrocytes in the brain of model mice, thereby inhibiting the release of inflammatory cytokines IL-6, IL-1β, TNF-α and improving stroke outcomes. Our results suggest that berberine may improve stroke outcomes by modulating the gut flora to increase the abundance of butyric acid. These findings elucidate the mechanisms by which berberine improves stroke outcomes and provide some basis for clinical treatment.
ARTICLE | doi:10.20944/preprints202310.1174.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: monotherapy; dual therapy; early ischemic stroke; efficacy; safety
Online: 18 October 2023 (11:44:35 CEST)
Objective: To analyze the clinical efficacy and safety of monotherapy and dual therapy in patients with early ischemic stroke. Methods: The study was conducted from August 2020 to August 2021, and 80 patients with early ischemic stroke who received treatment at our hospital during this period were selected as the study population. They were randomly divided into a control group and an observation group, with 40 patients in each group. The control group received conventional monotherapy, while the observation group received conventional dual therapy. The efficacy and safety indicators of the two groups were compared.Results: The treatment efficacy, functional recovery, blood indicators, and inflammation markers in the observation group were all superior to those in the control group (all, P<0.05); there was no significant difference in the drug safety profile between the two groups (P>0.05).Conclusion: The dual antiplatelet therapy is more ideal than monotherapy for treating patients with early ischemic stroke. It can further promote the recovery of neurological and cognitive function, improve hematological and inflammatory response indicators in patients, and the safety of this regimen is comparable to monotherapy.
ARTICLE | doi:10.20944/preprints202310.0314.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: Varicella-Zoster Virus; VZV; HIV; Stroke; Vascular risk
Online: 6 October 2023 (06:16:58 CEST)
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.
REVIEW | doi:10.20944/preprints202307.0880.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: inflammation; stroke; prognosis; positron emission tomography; recurrence; carotid
Online: 13 July 2023 (10:11:53 CEST)
Atherosclerosis is a chronic systemic inflammatory condition of the vasculature and a leading cause of stroke. Luminal stenosis severity is an important factor in determining vascular risk. Conventional imaging modalities, such as angiography or duplex ultrasonography, are used to quantify stenosis severity and inform clinical care but provide limited information on plaque biology. Inflammatory processes are central to atherosclerotic plaque progression and destabilization. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a validated technique for quantifying plaque inflammation. In this review, we discuss the evolution of FDG-PET as an imaging modality to quantify plaque vulnerability, challenges to standardization of image acquisition and analysis, its potential application to routine clinical care after stroke, and the possible role it will play in future drug discovery.
ARTICLE | doi:10.20944/preprints202304.0324.v1
Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: Egocentric neglect; Allocentric neglect; Stroke; Rehabilitation; Twins Therapy
Online: 13 April 2023 (12:44:13 CEST)
Abstract: (1) Background: existing treatment methods for neglect are concentrated on egocentric neglect and lead to various problems, such as cost/space constraints and portability. Therefore, this study seeks to determine how treatment (a.k.a., Twins Therapy, TT) can improve an existing problem in relation to neglect in stroke patients; (2) Method: The research design was a pre-post test control group design and both groups maintained existing rehabilitation treatment and added TT intervention only to the experimental group. TT intervention was conducted for a total of 20 sessions (1 session 30 min/day, 5 days/week for 4 weeks); (3) Result: as a result of comparison be-fore and after the TT intervention, there was no significant difference in MFT and MBI items (p>.05). However, the score and execution time of the Apple Cancellation Test showed significant reduction only in the experimental group (p<.05); (4) Conclusion: as a result of the study, TT im-proved not only egocentric neglect, but also allocentric neglect symptoms in stroke patients
CONCEPT PAPER | doi:10.20944/preprints202302.0421.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: stroke; aerobic exercise; cycling; moderate intensity; home-based
Online: 24 February 2023 (08:50:13 CET)
Objective: To investigate the feasibility and preliminary effects of a 12-week home-based moderate intensity cycling programme in stroke survivors. Design: Single-blinded, parallel group, Randomised Controlled Trial Setting: Home-based Participants: Participants will be survivors of first-ever stroke and randomly assigned to an Active Cycling Group (ACG) or control group. Intervention: The ACG performed a 12-week home-based cycling programme, three sessions per week. Work intervals were executed at 75% of the maximal heart rate (HRmax), recovery intervals at 50% of HRmax. Work interval duration increased from three ten-minute intervals to 30 minutes continuous cycling. The control group completed a 12-week neurocognitive exercise programme. Main outcome measurements: Primary outcome measures are compliance with training, adherence to protocol and safety as measured by adverse events. Secondary outcome measurements included a: simplified modified Rankin Scale questionnaire (stroke severity), Six-Minute Walking Test (walking ability), Ten-meter Walk Test (walking ability), Rivermead Mobility Index (walking ability), graded submaximal cycling test (exercise capacity), Physical Activity for Individuals with Physical Disability questionnaire (physical activity), EQ-5D-5L (quality of life), Stroke Specific Quality of Life questionnaire (quality of life), Montreal Cognitive Assessment (cognition), General Self-Efficacy Scale (self-efficacy), and Exercise Self-Regulation Questionnaire (self-regulation).
ARTICLE | doi:10.20944/preprints202209.0403.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Cell Disease; Stroke; Neuroimaging; Hematology; Computational fluid dynamics
Online: 27 September 2022 (02:38:29 CEST)
The main objective of this study is to demonstrate proof of principle that computational fluid dynamics (CFD) modeling is a tool for studying the contribution of covert and overt vascular architecture to the risk of cerebrovascular disease in in sickle cell disease (SCD) as well as uncover one or more mechanism of response to therapy such as chronic red blood cell (cRBC) transfusion. We analyzed baseline (screening), pre-randomization and study exit magnetic resonance angiogram (MRA) images from 10 (5 each from the transfusion and observation arms) pediatric sickle SCD participants in the silent cerebral infarct transfusion (SIT) trial, using CFD modeling. We reconstructed the intracranial portion of the internal carotid artery and branches and extracted the geometry using 3D Slicer. We cut specific potions of the large intracranial artery to include segments of the internal carotid, middle, anterior, and posterior cerebral artery such that the vessel segment analyzed extended from the intracranial beginning of the internal carotid artery up to immediately after (~0.25 inches) the middle cerebral artery branching point. Cut models were imported into Ansys 2021R2/2022R1 and laminar and time-dependent flow simulation was performed. Change in time averaged mean velocity, wall shear stress, and vessel tortuosity were compared between the observation and cRBC arm. We did not observe a correlation between time averaged mean velocity (TAMV) and mean transcranial doppler (TCD) velocity at study entry. There was also no difference in change in time average mean velocity, wall shear stress (WSS), and vessel tortuosity between the observation and cRBC transfusion arms. WSS and TAMV were abnormal for 2 (developed TIA) out of the 3 participants (one participant had SCI) that developed neurovascular outcomes. CFD approaches allows for the evaluation of vascular topology and hemodynamics in SCD using MRA images. In this proof of principle study, we show that CFD could be a useful tool and we intend to carry out future studies with a larger sample to enable more robust conclusions.
ARTICLE | doi:10.20944/preprints202206.0175.v2
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: survey; emergency medical services; training; stroke; prehospital care
Online: 16 June 2022 (10:58:04 CEST)
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.
ARTICLE | doi:10.20944/preprints202110.0214.v1
Subject: Social Sciences, Psychology Keywords: depression, anxiety, stress, ischemic stroke, psychiatry, mental disorders
Online: 14 October 2021 (10:49:20 CEST)
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.
ARTICLE | doi:10.20944/preprints202106.0430.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: stroke awareness; hypertensive patients; community health center; Indonesia
Online: 16 June 2021 (09:35:30 CEST)
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.
REVIEW | doi:10.20944/preprints202102.0289.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Cytokine, Depression, Ischemia, Stroke, Apoptosis, Excitotoxicity, Onecosis, Inflammation,
Online: 11 February 2021 (16:46:06 CET)
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.
REVIEW | doi:10.20944/preprints202004.0453.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: neurology; clinical features; coronavirus; stroke; encephalitis; headache; delirium
Online: 25 April 2020 (02:36:21 CEST)
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.
ARTICLE | doi:10.20944/preprints201804.0037.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: brain vessel; ischemic stroke; non-valvular atrial fibrillation
Online: 3 April 2018 (11:07:39 CEST)
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
REVIEW | doi:10.20944/preprints202011.0334.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: antiplatelet; aspirin; clopidogrel; ischemic stroke; TIA; platelet function analysis; antiplatelet therapy modification; secondary stroke prevention; high on-treatment platelet reactivity
Online: 12 November 2020 (09:35:12 CET)
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.
ARTICLE | doi:10.20944/preprints201705.0192.v1
Subject: Engineering, Marine Engineering Keywords: two-stroke engine; uniflow scavenging; exhaust gas composition; two-stroke gas flow performance parameters; air-fuel ratio; air consumption factor/ratio
Online: 26 May 2017 (10:56:56 CEST)
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 AFRstoich. 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.
ARTICLE | doi:10.20944/preprints202310.1668.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: post-stroke; hyperbaric oxygen therapy; sequelae; feasibility; out-patient
Online: 25 October 2023 (16:14:17 CEST)
Keywords: Post-Stroke; Hyperbaric oxygen therapy; Sequelae; Feasibility; Out-patient.
INTERESTING IMAGES | doi:10.20944/preprints202308.1660.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Moyamoya disease, stroke, Circle of Willis, MR-Angiography, M.R.I
Online: 23 August 2023 (12:52:11 CEST)
Moyamoya disease is also termed a spontaneous obstruction of the arteries in the circle of Willis. It is recognized as the leading cause of ischemic and hemorrhagic stroke. The infrequent cause of stroke is radiologically characterized by the continuous progression of stenosis of the end portion of the bilateral internal carotid artery and compensatory capillaries collaterals. A 1yr old child was admitted to the pediatric I.C.U with a complaint of decreased sensorium, decreased food intake and decreased right upper and lower extremity movements past two days. He had a history of convulsions at seven months of age. He was diagnosed with Moyamoya disease on Magnetic Resonance cerebral angiography. The clinical findings on MR-Angiography show multiple collaterals noted around Circle of Willis, specifically around the posterior communicating artery, anterior communicating artery, posterior cerebral artery, bilateral lenticulostriate, thalamoperforating arteries and medialfrontobasal arteries, which is suggestive of Moyamoya disease. Magnetic resonance imaging of the brain shows Gyral diffusion restriction in a right fronto-parieto-temporal region with mild swelling. The above clinical findings on MR-angiography show the Moyamoya disease in 1year old male child. These clinical findings on MR-Angiography and M.R.I – brain and neck can help the clinician accurately diagnose and manage this rare case.
ARTICLE | doi:10.20944/preprints202307.0608.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Accelerometery; Energy expenditure; Stroke; Gait; Six-minute walking test
Online: 10 July 2023 (11:37:46 CEST)
Background: The aim of this study was to compare energy expenditure (EE) predicted by accelerometery (EEAcc) with indirect calorimetry (EEMETA) in individuals with hemiparesis. Methods: Twenty-four participants (12 with stroke and 12 healthy controls) performed a six-minute walk test (6MWT) during which EEMETA was measured using a portable indirect calorimetry system and EEACC was calculated using Bouten’s equation (1993) with data from a 3-axis accelerometer positioned between L3 and L4. Results: Median EEMETA was 9.85 [8.18;11.89] W·kg-1 in the stroke group, and 5.0 [4.56;5.46] W·kg-1 in the control group. Median EEACC was 8.57 [7.86;11.24] W·kg-1 in the control group and 8.2 [7.05;9.56] W·kg-1 in the stroke group. EEACC and EEMETA were not significantly correlated in either the control (p=0.8) or the stroke groups (p=0.06). The Bland-Altman method showed a mean difference of 1.77±3.65 W·kg-1 between EEACC and EEMETA in the stroke group and -2.08±1.59 W·kg-1 in the controls. Conclusions: The accuracy of the predicted EE, based on the accelerometer and the equations proposed by Bouten et al, is low in individuals with hemiparesis and impaired gait. This combination (sensor and Bouten's equation) is not yet suitable for use as a stand-alone measure in clinical practice for the evaluation of hemiparetic patients.
ARTICLE | doi:10.20944/preprints202305.1208.v1
Subject: Engineering, Aerospace Engineering Keywords: landing gear; variable stroke; test; displacement control; follow-up
Online: 17 May 2023 (08:21:52 CEST)
The fixed stroke fatigue test can not simulate the real load condition of the landing gear, and the variable stroke fatigue test has increasingly become the mainstream. A modular test device for fatigue test for aircraft landing gears was designed, the automatic control of the buffer stroke was realized with ectopic displacement control technology effectively, the horizontal loading cylinder could follow the wheel axis actively with the displacement active control technology, follow-up loading along the vertical direction was realized through constructing a polar coordinate system and making the load line automatic alignment, a split-type dummy wheel was designed to improve the loading accuracy, a booster cylinder was designed to realize the control loading of high pressure combined with the hydraulic control system. The test shows that the technical scheme meets the design requirements, and the fatigue test was completed successfully. The device for landing gear variable stroke fatigue testing can be applied to other landing gear static / fatigue tests.
REVIEW | doi:10.20944/preprints202211.0447.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: EEG; stroke; traumatic brain injury; neurorehabilitation; brain-machine interface
Online: 24 November 2022 (02:08:43 CET)
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.
ARTICLE | doi:10.20944/preprints202202.0093.v1
Subject: Computer Science And Mathematics, Information Systems Keywords: mHealth; App; Stroke; Caregiver; Usability; User Experience; Needs; Design
Online: 7 February 2022 (15:17:42 CET)
(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.
ARTICLE | doi:10.20944/preprints202109.0043.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: aphasia; acute ischemic stroke; length of stay; mRS; NIHSS
Online: 2 September 2021 (14:39:03 CEST)
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.
ARTICLE | doi:10.20944/preprints202102.0062.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Stroke; Periodontitis; Periodontal disease; protein-protein network interaction; Bioinformatics
Online: 1 February 2021 (16:45:13 CET)
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.
ARTICLE | doi:10.20944/preprints202311.0999.v1
Subject: Medicine And Pharmacology, Emergency Medicine Keywords: emergency department; ED time targets; acute ischemic stroke; rt-PA
Online: 16 November 2023 (02:32:20 CET)
Background and objectives: Although intravenous tissue plasminogen activator (rt-PA) has been shown to be effective in the treatment of acute ischemic stroke (AIS) only a small proportion of stroke patients receive this drug. Low administration rate is mainly due to delayed presentation of patients to the emergency department (ED) or lack of a stroke team/unit in most of the hospitals. So, the aim of this study is to analyze ED time targets and the rate of rt-PA intravenous administration after the initial admission of patients with AIS in an ED from a traditional healthcare center (without a neurologist or stroke team/unit). Methods: To analyze which factors, influence administration of rt-PA we split the general sample (n=202) in two groups: group No rt-PA (n=137) and group rt-PA (n=65) based on performing or no intravenous thrombolysis. Results: Analyzing ED time targets for all sample we found that the median onset-to-ED door time was 180 minutes (IQR, 120-217.5 minutes), door-to-physician time was 4 minutes (IQR, 3-7 minutes), door-to-CT time was 52 minutes (IQR, 48-55 minutes), and door-in-door-out time was 61 minutes (IQR, 59-65 minutes). ED time targets such as door-to physician time (p=0.245), door-to-CT time (p=0.219), door-to-door-out time (p=0.24), or NIHSS at admission to Neurology department (p=0.405), or NIHSS after 24 h (p=0.9) did not have a statistically significant effect on administration or no rt-PA treatment in patients included in our study. Only highest Door-to-CT time was statistically significantly correlated with death outcome. Conclusion: In our study, rt-PA administration rate was higher than expected. Statistically significant correlation between ED time targets was found between lower Onset-to-ED door time with administration of rt-PA treatment (p<0.001) and between highest Door-to-CT time and death outcome.
ARTICLE | doi:10.20944/preprints202311.0927.v1
Subject: Social Sciences, Psychology Keywords: mixed-method; modelling; peers; single-case design; self-efficacy; stroke
Online: 14 November 2023 (15:21:18 CET)
We used a mixed-method single-case experimental research design to examine the effect of modelling (peer versus non-peer) on exercise self-efficacy in stroke survivors who participated in a community-based exercise program. Quantitative data were obtained using a ABCA design: (A1) no model/baseline 1 (3 weeks); (B) peer model (6 weeks); (C) non-peer model (6 weeks); and (A2) no model/baseline 2 (3 weeks). Four participants completed self-efficacy questionnaires after each weekly session. Qualitative data were obtained using researcher diaries and two semi-structured interviews: after B and A2. Based on quantitative and qualitative results, participants reported higher exercise self-efficacy in the model conditions, with ratings appearing highest for the non-peer model. This finding could be due to a lack of full integration of the peer model and low feelings of similarity. Modelling in general could help people recovering from a stroke increase their exercise self-efficacy, but non-peer models may not be most advantageous.
ARTICLE | doi:10.20944/preprints202309.1491.v1
Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: Blood-brain barrier; Brain ischaemia; Stroke; Biomarker; Tight Junction protein
Online: 21 September 2023 (12:16:03 CEST)
The blood-brain barrier (BBB) acts as a specialized structure separating the brain from peripheral blood circulation and plays an important role in brain function. Following an ischaemic stroke or cerebral ischaemia, the BBB is damaged leading to degraded proteins being released into blood circulation. However, little is known about cerebral ischaemia and reperfusion (I/R) induced BBB damage and changes in circulatory biomarkers. This study aims to use both immunohistochemistry and western blotting (WB) to examine neuronal death, glial cell alterations and changes in BBB tight junction (TJ) proteins such as zonula occludens-1 (ZO-1), Occludin and Claudin-5 in the hippocampus in a murine model of cerebral I/R. The changes in these proteins in the blood serum of this model were assessed by enzyme-linked immunosorbent assay. The results showed neuronal death and a significant increase in glial fibrillary acidic protein (GFAP), a protein primarily expressed in astrocytes and a significant decrease in TJ proteins, ZO-1, Occludin and Claudin-5 in the hippocampus of occluded mice as compared to sham-operated mice. These changes are associated with an increased level of these proteins in blood serum in ischaemic mice, suggesting that these proteins can be used as potential biomarkers for determining ischaemic stroke.
REVIEW | doi:10.20944/preprints202308.0445.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Acute ischemic stroke; AIS; radiomics; artificial intelligence; AI; neuroradiology; neurology.
Online: 4 August 2023 (13:20:17 CEST)
Acute ischemic stroke (AIS) is the loss of neurological function due to a sudden reduction in cerebral blood flow and is a leading cause of disability and death worldwide. In recent years, the field of radiological imaging has experienced an explosion that may reach unprecedented heights with the advent of artificial intelligence. One of the latest innovations in artificial intelligence is radiomics, which is based on the fact that a large amount of quantitative data can be extracted from radiological images, from which patterns can be identified and associated with specific pathologies. Since its inception, radiomics has been particularly associated with the field of oncology, with promising results in a wide range of clinical situations. The performance of radiomics in non-tumour pathologies has been increasingly explored in recent years and the results continue to be promising. The aim of this review is to explore the potential applications of radiomics in AIS patients and to theorise how radiomics may change the paradigm for these patients in the coming years.
ARTICLE | doi:10.20944/preprints202307.2007.v1
Subject: Public Health And Healthcare, Health Policy And Services Keywords: stroke; cost; burden; direct healthcare cost; loss of productivity; QALY
Online: 31 July 2023 (05:04:42 CEST)
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
REVIEW | doi:10.20944/preprints202307.0500.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: vertebrates; arterial pressure; cardiac output; exercise; heart rate; stroke volume
Online: 7 July 2023 (15:39:26 CEST)
Exercise is the greatest stress for the cardiovascular system, not only for the human being but for the rest of vertebrates. For this reason, the cardiovascular response cannot be considered as only one “anthropocentric” meaning. The adjustment of cardiac output to exercise in the five large groups of vertebrates is highly variable. The response of the heart rate and the stroke volume as the main two basic factors that determine the increase in cardiac output is also highly variable. The difference in the range of heart rate is difficult to determine in many vertebrates, both at rest and maximum effort. The increase in stroke volume also differs among vertebrates. For example, while rainbow trout and leopard increase their stroke volume by increasing final diastolic volume (Frank Starling's law), humans do so at the expense of both increasing final diastolic volume and reducing final stroke volume (contractility). The variation in arterial pressure that occurs during exercise also differs considerably among vertebrates. Large differences in cardiovascular response between different vertebrates could be related to their habitat or living environment. This review aims to analyze the cardiovascular response to exercise, as the most common stress condition in vertebrates.
REVIEW | doi:10.20944/preprints202306.1863.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: atherosclerosis; stroke; carotid; stenosis; biomarker; plaque; lipid; inflammation; IL-6
Online: 27 June 2023 (11:00:33 CEST)
Intracranial and extracranial large artery atherosclerosis (LAA) are a main cause of ischemic stroke. Biomarkers may aid in the diagnosis of LAA and help to stratify patients´ risk of stroke. We performed a narrative review of the literature mainly published in the last five years with the aim of identifying biomarkers associated either with intracranial or extracranial LAA in humans. Several potential biomarkers of LAA mainly related to lipid pathways and inflammation have been studied. Diagnostic biomarkers of LAA were evaluated by measuring biomarkers levels in patients with LAA stroke and other stroke etiologies. Some biomarkers were associated with prognosis of LAA stroke as evaluated by the modified Rankin score. Increased levels of IL-6 and have been associated with the risk of progression of the atherosclerotic disease. Overall, in most studies, the results were not externally validated. External validation of these results is needed. In the future, biomarkers could be useful for the selection of patients for clinical trials. To adopt these biomarkers in clinical practice we will need robust multicentric studies proving their reproduci-bility and a clear practical applicability for their use.
ARTICLE | doi:10.20944/preprints202210.0382.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Hemiparetic stroke; Cortical Reorganization; Somatosensory Evoked Potentials; EEG; Sensorimotor System.
Online: 25 October 2022 (08:39:11 CEST)
The cortical motor system can be reorganized following a stroke, with an increasing recruitment of the contralesional hemisphere. However, it is unknown whether a similar hemispheric shift occurs in the somatosensory system to adapt to this motor change, and whether this is related to movement impairments. This proof-of-concept study assessed somatosensory evoked potentials (SEPs), P50 and N100, in hemiparetic stroke participants and age-matched controls using high-density electroencephalograph (EEG) recordings during tactile finger stimulation. The laterality index was calculated to determine hemispheric dominance of the SEP and re-confirmed with source localization. The study found that latencies of P50 and N100 were significantly delayed in stroke brains when stimulating the paretic hand. The amplitude of P50 was negatively correlated with Fügl-Meyer Upper Extremity Motor Score in stroke. Bilateral cortical responses were detected in stroke, while only contralateral cortical responses were shown in controls, resulting in a significant difference in the laterality index. These results suggested that somatosensory reorganization after stroke involves increased recruitment of ipsilateral cortical regions. This reorganization delays the latency of somatosensory processing after a stroke. This research provided new insights related to the somatosensory reorganization after stroke, which could enrich future hypothesis-driven therapeutic rehabilitation strategies from a sensory or sensory-motor perspective.
ARTICLE | doi:10.20944/preprints202201.0065.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Aquaporin-4; AQP4ex; Stroke; Ischemia; Astrocyte; Astrogliosis; Glial scar; Neuroinflammation
Online: 6 January 2022 (10:16:02 CET)
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.
REVIEW | doi:10.20944/preprints202109.0070.v1
Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: stroke; inflammation; neuro-immune; cytokines; hemostasis; coagulation; protein-protein interactions
Online: 3 September 2021 (15:11:00 CEST)
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.
ARTICLE | doi:10.20944/preprints202107.0446.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Age; Sex; Stroke Types; Outcomes; SEM; Tertiary Hospitals; Rivers State
Online: 20 July 2021 (11:45:13 CEST)
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.
ARTICLE | doi:10.20944/preprints202101.0604.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: 5STS; stroke; MCID; responsiveness; stages; severity level; gait speed; FAC
Online: 29 January 2021 (08:19:05 CET)
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.
REVIEW | doi:10.20944/preprints202011.0351.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Cell therapy; MCAO; Stroke; Genetic engineering; Growth factors; Stem cells
Online: 12 November 2020 (14:25:43 CET)
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.
REVIEW | doi:10.20944/preprints202311.0808.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: ischaemic stroke; endovascular treatment; radiology; CT; MRI; acute; large in-farcts
Online: 14 November 2023 (05:23:27 CET)
Endovascular therapy (EVT) has revolutionized the management of acute ischaemic strokes with large vessel occlusion, with emerging evidence suggesting its benefit also in large infarct core volume strokes. In the last 2 years, 4 randomised controlled trials have been published on this topic - RES-CUE-Japan-LIMIT, ANGEL-ASPECT, SELECT2 and TENSION, with overall results showing that EVT improves functional and neurological outcomes compared to medical management alone. This review seeks to summarise the recent evidence presented by these 4 trials and highlight some of the limitations of our current understanding on this topic.
ARTICLE | doi:10.20944/preprints202310.2093.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: 3-Meter Backward Walk Test, stroke, psychometric properties, construct validity, reliability
Online: 1 November 2023 (03:40:57 CET)
In the context of evaluating physical function in individuals with stroke, the 3-meter backward walk test (3MBWT) emerges as a potential tool of interest. The purpose of this study was to assess the test-retest reliability and construct validity of the 3MBWT and its correlation with falling incidents. Conducted in a neurological rehabilitation center, 35 ambulatory individuals with stroke were enrolled within a month post-stroke onset. These participants, with a Functional Ambulation Category score of ≥4, underwent the 3MBWT, Functional Gait Assessment (FGA), 10-Meter Walk Test (10MWT), and 6-Minute Walk Test (6MWT) three times by different physiotherapists. Results indicated the 3MBWT displayed high reliability (r=0.97-0.98) and showed significant construct validity with other established walking tests like the 6MWT (r=-0.78) and 10MWT (r=0.71), with a moderate correlation to the FGA (r=-0.54). No marked differences in test outcomes were observed between participants based on their fall history. Conclusively, the 3MBWT proves to be highly reliable and validates well with existing walking function assessments for stroke patients, suggesting its potential as a time-efficient alternative.
REVIEW | doi:10.20944/preprints202310.1301.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Physiotherapy; neurorehabilitation; gait; transcranial electrical stimulation; stroke; non-invasive stimulation techniques
Online: 19 October 2023 (20:18:19 CEST)
Introduction: The transcranial direct current stimulation (tDCS) is a promising technique for brain modulation after cerebrovascular accident (CVA). This treatment modality has been previously studied in the recovery of patients. The aim of this review is to analyze the evidence in the ap-plication of tDCS in the recovery of gait disturbance in stroke patients. Methods: This review was conducted according to the recommendations of the PRISMA statement. Three different elec-tronic databases were searched for relevant results: PubMed, Scopus, and Cochrane. We included reviews and meta-analyses that only considered randomized controlled trials (RCTs) that inves-tigated the effects of transcranial direct electrical stimulation, in combination or not with other physiotherapy treatment, on gait recovery. Results: Thirteen studies with a total of 195 RCTs were included. Data on population, outcome measures, protocols and outcomes were extracted. The Amstar-2 scale and the GRADE system of certainty of evidence were used. Only one study re-ceived high certainty of evidence, 5 received low certainty of evidence and 7 received critically low certainty of evidence. Conclusions: Although the tDCS produces positive changes in gait recovery in spatio-temporal parameters, mobility, endurance, strength and motor function, there is insuf-ficient evidence to recommend this treatment.
ARTICLE | doi:10.20944/preprints202309.1564.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: nitric oxide, cooper, brain stroke, spinal cord injury, electron paramagnetic resonance
Online: 22 September 2023 (10:21:10 CEST)
Here we performed a comparative experimental analysis by EPR spectroscopy of the intensity of nitric oxide (NO) production and copper content in the injured and uninjured areas of the frontal lobes and the hippocampus of the brain of male Wistar rats, after modeling of combined brain and spinal cord injury. Brain and spinal cord injury were modelled by local destruction of the left precentral region of the brain using a stylet followed by hemorrhage injury at the level of the first lumbar vertebra of the spinal cord. We found a significant decrease in NO production 7 days after injury modeling in the injured and uninjured (contralateral) brain regions, but the copper content remained unchanged one week after injury modeling. Thus, combined brain and spinal cord injury is not accompanied by a radical change in the activity of the antioxidant system in the brain, which is also confirmed by the absence of changes in NO production and copper content in the hippocampus.
REVIEW | doi:10.20944/preprints202305.0865.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: OSAS; CPAP; diabetes mellitus; hypertension; ischemic heart disease; stroke; renal failure
Online: 11 May 2023 (13:47:41 CEST)
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.
ARTICLE | doi:10.20944/preprints202205.0038.v1
Subject: Public Health And Healthcare, Other Keywords: COVID-19; spinal cord injury; disability; stroke; well-being; social isolation
Online: 5 May 2022 (12:35:32 CEST)
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.
ARTICLE | doi:10.20944/preprints202203.0311.v1
Subject: Medicine And Pharmacology, Orthopedics And Sports Medicine Keywords: robot-assisted gait training; rehabilitation; stroke; cardiorespiratory fitness; robotics; disability; locomotion
Online: 23 March 2022 (08:40:16 CET)
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.
REVIEW | doi:10.20944/preprints202012.0544.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: adult neurogenesis; brain injury; neural stem cell; regeneration; stroke; zebrafish; mice
Online: 22 December 2020 (08:49:39 CET)
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.
COMMUNICATION | doi:10.20944/preprints202011.0404.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Cerebral vasculature; vascular fractionation protocol; neurovascular niche; blood-brain barrier; stroke
Online: 16 November 2020 (09:06:38 CET)
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.
REVIEW | doi:10.20944/preprints201910.0135.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: acupuncture; dysphagia; post-acute stroke; overview; systematic reviews; meta-analyses; rehabilitation
Online: 12 October 2019 (03:31:46 CEST)
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
ARTICLE | doi:10.20944/preprints202311.0612.v1
Subject: Engineering, Civil Engineering Keywords: Superelstic SMA; honeycomb damper; geometrical nonlinear property; long-stroke; thickness of walls
Online: 9 November 2023 (11:25:22 CET)
Despite the fact that SMA restrainers exhibit a superelastic strain capacity of 7%, this capacity appears inadequate for isolated bridges due to the typically greater than 20cm relative dis-placements between girders during intense seismic events. In order to perform such a stroke, a SMA restrainer of greater than 3 metres in length might be required. In order to reduce the length of restrainers, a novel honeycomb damper constructed from superelastic shape memory alloy (SMA) is proposed. The proposed device, denoted as the superelastic SMA honeycomb damper (SHD), is comprised of steel plates to prevent the SMA plane from collapsing and superelastic SMA honeycomb to provide self-centering capability. By incorporating the large strain capacity of SMA and the geometrically nonlinear deformation of honeycomb structures, SHD has been developed to satisfy the requirements of bridge restrainers with large strokes. It is capable of functioning as a restrainer and energy dissipation device when subjected to dynamic tension and compression loads. The SHD was initially investigated from a theoretical perspective. Following this, a mul-ti-cell SHD specimen was manufactured. The specimen underwent axial tensile and compressive experiments in order to examine the mechanical properties of SHDs. Finally, experimental results were investigated through numerical simulation analyses of the SHDs using a three-dimensional high-fidelity finite element model. Additionally, a method for enhancing SHD was proposed. The findings indicate that SHD is capable of exhibiting superior self-centering capability and sta-ble hysteretic responses when subjected to earthquakes.
REVIEW | doi:10.20944/preprints202311.0539.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: Citicoline; Medical Food; Acute Ischemic Stroke; Evidence-based Medicine; Philosophy of Science
Online: 8 November 2023 (13:49:03 CET)
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.
REVIEW | doi:10.20944/preprints202310.1068.v1
Subject: Medicine And Pharmacology, Otolaryngology Keywords: obstructive sleep apnea; head and neck cancer; hypermetabolic syndrome; cardiovascular deases; stroke
Online: 17 October 2023 (10:37:05 CEST)
Introduction and objectives Obstructive sleep apnea (OSA) is defined as a cause of daytime sleepiness, as well as a clinical manifestation of sleep-disordered breathing. In the literature, there are numerous controversial studies regarding the etiology of this condition, but it is universally accepted that a significant role in its onset is played by the reduced activity of the upper airway muscles. Additionally, OSA has been associated with a series of comorbidities, such as type II diabetes, metabolic syndrome, cardiovascular and pulmonary conditions, as well as head and neck tumors, especially oropharyngeal and laryngeal tumors. The purpose of this review is to examine and demonstrate the prevalence of OSA in patients with associated pathologies, especially in patients with head and neck tumors, as well as the role of surgical and non-surgical therapeutic methods in improving the quality of life. Material and methods Taking into consideration the stated objective, a systematic analysis of the available literature was conducted, encompassing PubMed, Medline and Scopus databases. The evaluation was based on several keywords, including head and neck cancer, diabetes, diabetic, overlap syndrome, cardiovascular conditions, laryngeal neoplasm, radiotherapy, chemotherapy, as well as the concept of quality of life in laryngectomized patients and patients with OSA. Results Our results demonstrate the involvement of OSA in the presence of comorbidities and also, an increased incidence of OSA in patients with laryngeal cancer. It is important to note that surgical and post-surgical treatment can play a significant role in triggering OSA in these patients. Conclusions The clinician must recognize the increased prevalence of OSA in patients with head and neck cancer, as well as the coexistence of OSA with certain comorbidities. They should actively engage in early diagnosis and establish optimal treatment methods to improve the quality of life for patients with associated conditions such as head and neck tumors or cardiovascular pathology.
ARTICLE | doi:10.20944/preprints202310.0409.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: Stroke; COVID-19; SARS-CoV-2 Omicron variant; modified Ranking scale; coagulopathy
Online: 9 October 2023 (09:30:50 CEST)
COVID-19 has rapidly spread worldwide since December 2019. During the pandemic, SARS-CoV-2 repeatedly mutated from Alpha to Omicron. The severity and mortality are related to age, sex, and underlying diseases (respiratory, cerebrovascular, cardiovascular, metabolic, cancer, and immune diseases). We retrospectively studied 44 hospitalized stroke patients infected with the SARS-CoV-2 Omicron variant. The mortality rate of hospitalized stroke patients with COVID-19 was 6 (13.6%). The cause of death was coagulopathy in 3 cases of ischemic stroke. High modified Rankin Scale score（mRS）of stroke patient was correlated with severity of COVID-19. The timing of vaccination is inversely correlated with COVID-19 severity. In conclusion, stroke patients with COVID-19 have high mortality rates attributed to coagulopathy. Stroke patients with high mRS scores are more likely to develop severe COVID-19. In high mRS scores, therapy for severe COVID-19 should be administered.
REVIEW | doi:10.20944/preprints202309.0100.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Post-Traumatic Stress Disorder, neurologic injury, traumatic brain injury, subarachnoid hemorrhage, stroke
Online: 4 September 2023 (15:39:56 CEST)
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.
ARTICLE | doi:10.20944/preprints202307.2117.v1
Subject: Engineering, Bioengineering Keywords: stroke; neurorehabilitation; arm rehabilitation robot; transparency; adaptive weight support; end-effector robot
Online: 1 August 2023 (03:29:32 CEST)
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.
ARTICLE | doi:10.20944/preprints202205.0184.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: amyloid precursor protein; photothrombotic stroke; ischemia; alpha-secretase; beta-secretase; gamma-secretase
Online: 13 May 2022 (08:39:09 CEST)
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.
ARTICLE | doi:10.20944/preprints202101.0303.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Controlling Nutritional Status Score; Hemorrhagic stroke; Nutrition screening; Prognosis; Modified Rankin Scale
Online: 15 January 2021 (16:08:15 CET)
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 < 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.