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Advances and Challenges in Stroke Therapy: A Regenerative Prospective

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A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Neurology".

Deadline for manuscript submissions: closed (31 July 2024) | Viewed by 21434

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Prof. Dr. Dejan Nikolić

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Guest Editor

1. Department of Physical Medicine and Rehabilitation, Faculty of Medicine, University Belgrade, 11000 Belgrade, Serbia
2. University Children's Hospital, 11000 Belgrade, Serbia
Interests: electrodiagnostics; rehabilitation; population genetics; physical activity
Special Issues, Collections and Topics in MDPI journals

Dr. Milena Janković

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Guest Editor

Neurology Clinic, University Clinical Center of Serbia, 11000 Belgrade, Serbia
Interests: neurogenetics; neurodegenerative disorders; stroke; movement disorders; mitochondrial disorders; pharmacogenetics

Special Issue Information

Dear Colleagues,

The multifactorial stroke etiology is creating the need for permanent development of novel and more specific therapies and treatments for pediatric and adult stroke patients. Decades of extensive research in the field of stroke accumulated a significant amount of evidence about inflammation influence in neuronal loss in stroke patients. On the contrary, the association between inflammation and repair processes in ischemic stroke is documented as well. Another important aspect in the recovery of patients after the stroke is genetic determinants that may have a role in complex stroke processes and genetic-dependent immunomodulation in stroke treatment.

In this Special Issue, we would like to highlight the connection between genetic factors, inflammation, and challenges in the development of next-generation therapeutics in stroke and how genetic prediction may advance the application of thrombolytic, antithrombotic, and neuroprotective interventions. Additionally, we would like to focus on therapies for balancing immune reaction and shifting activity from pro-inflammatory to anti-inflammatory, and from neurotoxic to neuroprotective.

The preferred type of manuscripts would be: Reviews, Systematic Reviews, Meta-analyses, Original articles, Evidence-based papers, Guidelines, Recommendations, and Case studies.

Prof. Dr. Dejan Nikolić
Dr. Milena Janković
Guest Editors

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Keywords

stroke
next generation therapeutics
neuroprotection
neuroregeneration
immunomodulation
genetic predisposition
inflammation

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Published Papers (9 papers)

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Research

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13 pages, 4170 KiB

Open AccessArticle

An Evaluation of the Effectiveness of Melatonin and n-Acetylcysteine in Cerebral Ischemia-Reperfusion Injury in Adult Rats

by Hilal Aydin, Ozgur Bulmus, Oguzhan Korkut, Eren Altun and Ali Engin Ulusal

Medicina 2023, 59(11), 2026; https://doi.org/10.3390/medicina59112026 - 17 Nov 2023

Cited by 2 | Viewed by 1851

Abstract

Background and Objectives: The purpose of this study was to apply histopathological and immunohistochemical methods to compare the protective efficacy of melatonin and N-acetylcysteine (NAC) application in rats with experimental brain ischemia/reperfusion (I/R) injury induced through occlusion of the middle cerebral artery (MCA), and to evaluate the protective effect of their combined use. Materials and Methods: Forty-one young adult male Wistar albino rats were divided into five groups—control (n = 8), I/R group (n = 8), melatonin (n = 8), NAC (n = 8), and melatonin + NAC (n = 9). Results: All scores differed between the groups, apart from vascular congestion (p < 0.05). At two-way comparisons, all histological scores were significantly higher in the I/R group than in the control group (p < 0.05). No change occurred in the vascular congestion scores with the administration of melatonin, although decreases were determined in all other scores. These decreases were statistically significant for cellular eosinophilic pyknotic degeneration, vacuolization, and edema (p < 0.05). All histopathological scores in the group administered NAC together with melatonin were significantly lower than in the I/R group (p < 0.05). Conclusions: The combined use of NAC and melatonin, the neuroprotective efficacy of which on histopathological parameters is shown in this study, now needs to be supported by further research. Full article

(This article belongs to the Special Issue Advances and Challenges in Stroke Therapy: A Regenerative Prospective)

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11 pages, 950 KiB

Open AccessArticle

Implicit Motor Learning Strategies Benefit Dual-Task Performance in Patients with Stroke

by Eito Arikawa, Masatomo Kubota, Tomoko Haraguchi, Masachika Takata and Shoji Natsugoe

Medicina 2023, 59(9), 1673; https://doi.org/10.3390/medicina59091673 - 16 Sep 2023

Cited by 1 | Viewed by 1977

Abstract

Background and Objectives: In stroke rehabilitation, the use of either implicit or explicit learning as a motor learning approach during dual tasks is common, but it is unclear which strategy is more beneficial. This study aims to determine the benefits of implicit versus explicit motor learning approaches in patients with stroke. Materials and Methods: Seventeen patients with stroke and 21 control participants were included. Motor learning was evaluated using the Serial Reaction Time Task (SRTT) in the context of dual-task conditions. The SRTT was conducted on two separate days: one day for implicit learning conditions and the other day for explicit learning conditions. Under the explicit learning conditions, a task rule was given to the participants before they started the task, but not under the implicit learning conditions. Learning scores were calculated for both implicit and explicit learning, and these scores were then compared within groups for patients with stroke and controls. We calculated the difference in learning scores between implicit and explicit learning and conducted a correlation analysis with the Trail Making Test (TMT) Parts A and B. Results: Learning scores on the SRTT were not different between implicit and explicit learning in controls but were significantly greater in patients with stroke for implicit learning than for explicit learning. The difference in learning scores between implicit and explicit learning in patients with stroke was correlated with TMT-A and showed a correlation trend with TMT-B. Conclusions: Implicit learning approaches may be effective in the acquisition of motor skills with dual-task demands in post-stroke patients with deficits in attention and working memory. Full article

(This article belongs to the Special Issue Advances and Challenges in Stroke Therapy: A Regenerative Prospective)

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13 pages, 797 KiB

Open AccessArticle

Effect of Virtual Reality Therapy on Quality of Life and Self-Sufficiency in Post-Stroke Patients

by Marcela Dąbrowská, Dalibor Pastucha, Miroslav Janura, Hana Tomášková, Lucie Honzíková, Šárka Baníková, Michal Filip and Iva Fiedorová

Medicina 2023, 59(9), 1669; https://doi.org/10.3390/medicina59091669 - 15 Sep 2023

Cited by 6 | Viewed by 2970

Abstract

Background and Objectives: The consequences of stroke have a significant impact on self-sufficiency and health-related quality of life (HRQoL). Virtual reality (VR)-based rehabilitation has the potential to impact these modalities, but information on timing, volume, and intensity is not yet available. The aim of this randomized controlled trial (1:1) was to evaluate the impact of conventional rehabilitation combined with VR on self-care and domains of HRQoL in patients ≤6 months post-stroke. Materials and Methods: The intervention group completed a total of 270 min of conventional VR + rehabilitation sessions. The control group underwent conventional rehabilitation only. Primary assessments with the WHO disability assessment schedule 2.0 (WHODAS 2) questionnaire were conducted before rehabilitation (T0), after completion of the intervention (T1), and at the 4-week follow-up (T2); secondary outcomes included self-sufficiency and balance assessments. Results: Fifty patients completed the study (mean age 61.2 ± 9.0 years, time since stroke 114.3 ± 39.4 days). There were no statistically significant differences between the groups in WHODAS 2, self-sufficiency, and balance scores (p > 0.05). Conclusions: In the experimental group, there was a statistically significant difference in WHODAS 2, assessment of self-sufficiency, and balance scores before and after therapy (p < 0.05). VR appears to be a suitable tool to supplement and modify rehabilitation in patients after stroke. Full article

(This article belongs to the Special Issue Advances and Challenges in Stroke Therapy: A Regenerative Prospective)

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8 pages, 2736 KiB

Open AccessArticle

Essential Thrombocythemia and Ischemic Stroke: A Case Series of Five JAK2-Positive Patients

by Byong-Kyu Kim, Kyung Yoon Eah and Jin-Mo Park

Medicina 2023, 59(7), 1300; https://doi.org/10.3390/medicina59071300 - 14 Jul 2023

Cited by 1 | Viewed by 2060

Abstract

Background and Objectives: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by elevated platelet counts and an increased risk of thrombotic events, including ischemic strokes. Materials and 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. Full article

(This article belongs to the Special Issue Advances and Challenges in Stroke Therapy: A Regenerative Prospective)

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17 pages, 1912 KiB

Open AccessArticle

Extended Poststroke Rehabilitation Combined with Cerebrolysin Promotes Upper Limb Motor Recovery in Early Subacute Phase of Rehabilitation: A Randomized Clinical Study

by Sindi Z. Mitrović, Ljubica M. Konstantinović, Vera Miler Jerković, Suzana Dedijer-Dujović and Olivera C. Djordjević

Medicina 2023, 59(2), 291; https://doi.org/10.3390/medicina59020291 - 3 Feb 2023

Cited by 1 | Viewed by 2574

Abstract

Background and Objectives: The recovery of stroke patients with severe impairment is usually poor and limited and, unfortunately, under-investigated in clinical studies. In order to support neuroplasticity and modulate motor recovery, Cerebrolysin combined with rehabilitation treatment has proven effective in the acute stroke phase in moderate to severe motor impairment. The aim of this study was to determine the efficacy of extended poststroke rehabilitation combined with Cerebrolysin on upper limb motor recovery in subacute stroke patients with severe upper limb motor impairment. Materials and Methods: A randomized, double-blind, placebo-controlled study was conducted. Sixty patients at the early stage of severe sub-acute stroke who fulfilled all eligibility criteria were randomly assigned to the Cerebrolysin group or placebo group (𝑛 = 30 each). Both groups, after conducting three weeks of conventional rehabilitation treatment five days per week, continued to perform conventional rehabilitation treatment three times per week until 90 days of rehabilitation treatment. The primary outcome measure was the Action Research Arm Test (ARAT), and the secondary outcomes were the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) motor score, Barthel index (BI), and the National Institutes of Health Stroke Scale (NIHSS). The outcome data were evaluated before, after three weeks of treatment, and on the 90th day of rehabilitation treatment, and compared within groups and between the two groups. There were no adverse events. Results: Both groups showed a significant improvement (p < 0.001) over time in BI, FMA-UE, ARAT, and NIHSS scores. Patients receiving Cerebrolysin showed more significant improvement in post-stroke upper limb motor impairment and functioning compared to the placebo group after only three weeks, and the trend was maintained after 90 days of follow up. Conclusion: Cerebrolysin delivered in the early subacute post-stroke phase added to extended conventional rehabilitation treatment is beneficial and improves motor functional recovery in patients with severe motor impairment, especially on the paretic upper extremity. Full article

(This article belongs to the Special Issue Advances and Challenges in Stroke Therapy: A Regenerative Prospective)

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9 pages, 312 KiB

Open AccessArticle

Endovascular Treatment of Basilar Artery Occlusion: What Can We Learn from the Results?

by Aleksandra Ekkert, Une Jokimaitytė, Valerija Tutukova, Givi Lengvenis, Rytis Masiliūnas and Dalius Jatužis

Medicina 2023, 59(1), 96; https://doi.org/10.3390/medicina59010096 - 31 Dec 2022

Cited by 1 | Viewed by 1878

Abstract

Background and Objectives: Current guidelines lack specific endovascular treatment (EVT) recommendations for posterior circulation stroke (PCS). The results of earlier studies are controversial. We aimed to compare early hospital outcomes of stroke caused by large-vessel occlusion (LVO) treated with EVT or bridging therapy (BT) in anterior circulation stroke (ACS) versus PCS (middle cerebral artery occlusion (MCAO) and basilar artery occlusion (BAO), and establish the risk factors for poor outcome. Materials and Methods: we analyzed the data of 279 subjects treated with EVT due to LVO-caused stroke in a comprehensive stroke centre in 2015–2021. The primary outcome was hospital mortality, secondary outcomes were National Institutes of Health Stroke Scale (NIHSS) after 24 h, early neurological deterioration, futile recanalization (FR), the ambulatory outcome at discharge, and complications. Results: BAO presented with higher baseline NIHSS scores (19 vs. 14, p < 0.001), and longer door-to-puncture time (93 vs. 82 min, p = 0.034), compared to MCAO. Hospital mortality and the percentage of FR were the same in BAO and almost two times higher than in MCAO (20.0% vs. 10.3%, p = 0.048), other outcomes did not differ. In BAO, unsuccessful recanalization was the only significant predictor of the lethal outcome, though there were trends for PAD and RF predicting lethal outcome. A trend for higher risk of symptomatic intracranial hemorrhage (sICH) was observed in the BAO group when BT was applied. Nevertheless, neither BT nor sICH predicted lethal outcomes in the BAO group. Conclusions: Compared to the modern gold standard of EVT in the ACS, early outcomes in BAO remain poor, there is a substantial amount of FR. Nevertheless, unsuccessful recanalization remains the strongest predictor of lethal outcomes. BT in PCS might pose a higher risk for sICH, but not the lethal outcome, although this finding requires further investigation in larger trials. Full article

(This article belongs to the Special Issue Advances and Challenges in Stroke Therapy: A Regenerative Prospective)

12 pages, 326 KiB

Open AccessArticle

Postacute Rehabilitation Impact on Functional Recovery Outcome and Quality of Life in Stroke Survivors: Six Month Follow-Up

by Emir Bisevac, Milica Lazovic, Dejan Nikolic, Elvis Mahmutovic, Zana Dolicanin and Aleksandra Jurisic-Skevin

Medicina 2022, 58(9), 1185; https://doi.org/10.3390/medicina58091185 - 30 Aug 2022

Cited by 2 | Viewed by 2232

Abstract

Background and Objectives: This study aimed to examine the impact of postacute rehabilitation duration on the outcome of the functional recovery and patients’ quality of life after the stroke. Materials and Methods: One hundred patients (52 females, 48 males, mean age: 66.5 ± 7.3; range 53 to 79 years) who experienced a stroke (50 with ischemic stroke (IS) and 50 with intracranial hemorrhage (ICH)) took part in the study. Patients (treated with postacute rehabilitation measures for six months) were examined after one, three, and six months of postacute rehabilitation. Functional independence was measured using the functional independence measure (FIM) test, while the EQ-5D-3L questionnaire was used to assess the quality of life. Results: Patients with ICH had a slightly lower FIM score (FIM motor = 29.8 ± 11.8; FIM cognitive = 14.4 ± 4.6) on admission compared to patients with IS (FIM motor = 41.8 ± 18.8; FIM cognitive = 18.7 ± 6.3), but, after six months of postacute rehabilitation, patients with ICH reached an approximate level of functional independence (FIM motor = 53.8 ± 14.4; FIM cognitive = 25.8 ± 4.7), as did patients with IS (FIM motor = 67.6 ± 16.4; FIM cognitive = 29.2 ± 4.0). The motor and cognitive FIM, as well as quality of life, was statistically significantly increased at all four measurement points (p < 0.001). Furthermore, there is a statistically significant connection between functional independence and quality of life at all tested times. Conclusion: Patients achieved the highest degree of functional independence after six months. Furthermore, our findings point out that inpatient rehabilitation as well as outpatient rehabilitation are effective in functionality and quality of life improvement after a stroke; thus, both should be emphasized and regularly implemented. Full article

(This article belongs to the Special Issue Advances and Challenges in Stroke Therapy: A Regenerative Prospective)

Review

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14 pages, 1037 KiB

Open AccessReview

Stroke vs. Preeclampsia: Dangerous Liaisons of Hypertension and Pregnancy

by Milan Lackovic, Dejan Nikolic, Milena Jankovic, Marija Rovcanin and Sladjana Mihajlovic

Medicina 2023, 59(10), 1707; https://doi.org/10.3390/medicina59101707 - 24 Sep 2023

Cited by 6 | Viewed by 3131

Abstract

Stroke during pregnancy and preeclampsia are two distinct but interrelated medical conditions, sharing a common denominator—blood control failure. Along with cardiovascular diseases, diabetes, dyslipidemia, and hypercoagulability, hypertension is undoubtedly a major risk factor associated with stroke. Even though men have higher age-specific stroke rates, women are facing higher life-long stroke risk, primarily due to longer life expectancy. Sex hormones, especially estrogen and testosterone, seem to play a key link in the chain of blood pressure control differences between the genders. Women affected with stroke are more susceptible to experience some atypical stroke manifestations, which might eventually lead to delayed diagnosis establishment, and result in higher morbidity and mortality rates in the population of women. Preeclampsia is a part of hypertensive disorder of pregnancy spectrum, and it is common knowledge that women with a positive history of preeclampsia are at increased stroke risk during their lifetime. Preeclampsia and stroke display similar pathophysiological patterns, including hypertension, endothelial dysfunction, dyslipidemia, hypercoagulability, and cerebral vasomotor reactivity abnormalities. High-risk pregnancies carrying the burden of hypertensive disorder of pregnancy have up to a six-fold higher chance of suffering from stroke. Resemblance shared between placental and cerebral vascular changes, adaptations, and sophisticated auto-regulatory mechanisms are not merely coincidental, but they reflect distinctive and complex cardiovascular performances occurring in the maternal circulatory system during pregnancy. Placental and cerebral malperfusion appears to be in the midline of both of these conditions; placental malperfusion eventually leads to preeclampsia, and cerebral to stoke. Suboptimal performances of the cardiovascular system are proposed as a primary cause of uteroplacental malperfusion. Placental dysfunction is therefore designated as a secondary condition, initiated by the primary disturbances of the cardiovascular system, rather than an immunological disorder associated with abnormal trophoblast invasion. In most cases, with properly and timely applied measures of prevention, stroke is predictable, and preeclampsia is a controllable condition. Understanding the differences between preeclampsia and stroke in pregnancy is vital for healthcare providers to enhance their clinical decision-making strategies, improve patient care, and promote positive maternal and pregnancy outcomes. Management approaches for preeclampsia and stroke require a multidisciplinary approach involving obstetricians, neurologists, and other healthcare professionals. Full article

(This article belongs to the Special Issue Advances and Challenges in Stroke Therapy: A Regenerative Prospective)

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Other

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6 pages, 524 KiB

Open AccessCase Report

A New Neurological Screening Approach for Diagnosing Brainstem Infarction Using the Calling Method and Familiar Voices

by Yuzuru Ohshiro

Medicina 2023, 59(7), 1344; https://doi.org/10.3390/medicina59071344 - 21 Jul 2023

Viewed by 1561

Abstract

This report proposes a new approach to assess dysarthria in patients with brainstem infarction by involving familiar individuals. Collaboration provides valuable insights compared to subjective traditional methods. A man in his 70s presented with resolved positional vertigo. Standard neurological tests showed no abnormalities, and inquiries with the patient’s friend did not reveal voice changes. While inquiring about voice changes with family, friends, and acquaintances is a common practice in clinical settings, our approach involved the patient calling out to his friend from a distance. Despite the physician detecting no abnormalities, the friend noticed a lower voice. Subsequent magnetic resonance imaging (MRI) confirmed brainstem infarction. Early and subtle symptoms of brainstem infarction pose a detection challenge and can lead to serious outcomes if overlooked. This report provides the first evidence that distance calling can detect subtle voice changes associated with brainstem infarction potentially overlooked by conventional neurological examinations, including inquiries with individuals familiar with the patient’s voice. Detecting brainstem infarction in emergency department cases is often missed, but conducting MRIs on every patient is not feasible. This simple method may identify patients overlooked by conventional screening who should undergo neuroimaging such as MRI. Further research is needed, and involving non-professionals in assessments could significantly advance the diagnostic process. Full article

(This article belongs to the Special Issue Advances and Challenges in Stroke Therapy: A Regenerative Prospective)

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