Neurology International

19 pages, 8489 KiB

Open AccessArticle

Hypomyelinating Leukodystrophy 10 (HLD10)-Associated Mutations of PYCR2 Form Large Size Mitochondria, Inhibiting Oligodendroglial Cell Morphological Differentiation

by Tomohiro Torii, Remina Shirai, Risa Kiminami, Satoshi Nishino, Takanari Sato, Sui Sawaguchi, Nana Fukushima, Yoichi Seki, Yuki Miyamoto and Junji Yamauchi

Neurol. Int. 2022, 14(4), 1062-1080; https://doi.org/10.3390/neurolint14040085 - 16 Dec 2022

Cited by 3 | Viewed by 2461

Abstract

Hypomyelinating leukodystrophy 10 (HLD10) is an autosomal recessive disease related to myelin sheaths in the central nervous system (CNS). In the CNS, myelin sheaths are derived from differentiated plasma membranes of oligodendrocytes (oligodendroglial cells) and surround neuronal axons to achieve neuronal functions. Nucleotide [...] Read more.

Hypomyelinating leukodystrophy 10 (HLD10) is an autosomal recessive disease related to myelin sheaths in the central nervous system (CNS). In the CNS, myelin sheaths are derived from differentiated plasma membranes of oligodendrocytes (oligodendroglial cells) and surround neuronal axons to achieve neuronal functions. Nucleotide mutations of the pyrroline-5-carboxylate reductase 2 (PYCR2) gene are associated with HLD10, likely due to PYCR2’s loss-of-function. PYCR2 is a mitochondrial residential protein and catalyzes pyrroline-5-carboxylate to an amino acid proline. Here, we describe how each of the HLD10-associated missense mutations, Arg119-to-Cys [R119C] and Arg251-to-Cys [R251C], lead to forming large size mitochondria in the FBD-102b cell line, which is used as an oligodendroglial cell differentiation model. In contrast, the wild type proteins did not participate in the formation of large size mitochondria. Expression of each of the mutated R119C and R251C proteins in cells increased the fusion abilities in mitochondria and decreased their fission abilities relatively. The respective mutant proteins, but not wild type proteins also decreased the activities of mitochondria. While cells expressing the wild type proteins exhibited differentiated phenotypes with widespread membranes and increased expression levels of differentiation marker proteins following the induction of differentiation, cells harboring each of the mutant proteins did not. Taken together, these results indicate that an HLD10-associated PYCR2 mutation leads to the formation of large mitochondria with decreased activities, inhibiting oligodendroglial cell morphological differentiation. These results may reveal some of the pathological mechanisms in oligodendroglial cells underlying HLD10 at the molecular and cellular levels. Full article

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16 pages, 2076 KiB

Open AccessReview

EEG in Neurorehabilitation: A Bibliometric Analysis and Content Review

by Athanasia Tsiamalou, Efthimios Dardiotis, Konstantinos Paterakis, George Fotakopoulos, Ioannis Liampas, Markos Sgantzos, Vasileios Siokas and Alexandros G. Brotis

Neurol. Int. 2022, 14(4), 1046-1061; https://doi.org/10.3390/neurolint14040084 - 16 Dec 2022

Cited by 9 | Viewed by 3048

Abstract

Background: There is 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. [...] Read more.

Background: There is 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. We used the most influential papers to outline the knowledge base and carried out a word co-occurrence analysis to identify the research hotspots. We also used depicted collaboration networks between universities, authors, and countries after analyzing the cocitations. The results were presented in summary tables, plots, and 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 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 L.F. Nicolas-Alfonso and J. Gomez-Gill, with 997 citations, followed by “Brain-computer interfaces in neurological rehabilitation” by J. Daly and J.R. Wolpaw (708 citations). The US, 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 (BCIs) and can be successfully used in the neurorehabilitation of patients with stroke symptoms, amyotrophic lateral sclerosis, and traumatic brain and spinal injuries. EEG-based BCI facilitates the 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. Full article

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Graphical abstract

10 pages, 876 KiB

Open AccessArticle

The Effect of Trunk Position on Attentional Disengagement in Unilateral Spatial Neglect

by Kohei Shida, Kazu Amimoto, Kazuhiro Fukata, Shinpei Osaki, Hidetoshi Takahashi and Shigeru Makita

Neurol. Int. 2022, 14(4), 1036-1045; https://doi.org/10.3390/neurolint14040083 - 13 Dec 2022

Cited by 1 | Viewed by 1669

Abstract

Unilateral spatial neglect (USN) causes difficulties in disengaging attention from the right side to unexpected targets on the left. However, the relationship between egocentric spatial position and attentional disengagement remains unclear. Therefore, this study aimed to clarify the relationship between trunk position and [...] Read more.

Unilateral spatial neglect (USN) causes difficulties in disengaging attention from the right side to unexpected targets on the left. However, the relationship between egocentric spatial position and attentional disengagement remains unclear. Therefore, this study aimed to clarify the relationship between trunk position and attentional disengagement. Thirty-eight patients with early stroke onset were classified as follows: USN (n = 18), right brain damage without USN (n = 10), and left brain damage (n = 10). The primary outcome was reaction time (RT) in the modified Posner task (MPT). The MPT comprised a condition in which the preceding cue and target direction were the same (valid condition) and a condition in which the directions were opposite (invalid condition). RT to the target was calculated. The MPT was performed in three different trunk positions (trunk midline, left, and right). In each group, the RT was compared on the basis of the stimulus conditions and trunk position. The RT was delayed in the valid and invalid left conditions, especially in the invalid left condition. The RT of the trunk right condition was significantly reduced compared with that of trunk midline and left conditions in the invalid left condition. Thus, trunk position influences attentional disengagement. This study contributes to the rehabilitation of patients with neglect symptoms. Full article

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12 pages, 2420 KiB

Open AccessArticle

Safety of Deep Repetitive Transcranial Magnetic Stimulation (drTMS) against Medical Refractory Symptoms in Parkinson Syndromes: First German Real-World Data with a Specific H5 Coil

by Celine Cont, Annaliis Lehto, Nathalie Stute, Anastasia Galli, Christina Schulte, Veronika Deer, Michaela Wessler and Lars Wojtecki

Neurol. Int. 2022, 14(4), 1024-1035; https://doi.org/10.3390/neurolint14040082 - 12 Dec 2022

Cited by 2 | Viewed by 2651

Abstract

So far, deep repetitive transcranial magnetic stimulation (drTMS) has shown promising results as an add-on treatment for Parkinson’s disease (PD) but not for non-idiopathic Parkinson Syndromes (PS). We aimed to investigate the safety and feasibility of drTMS application in patients with different Parkinson [...] Read more.

So far, deep repetitive transcranial magnetic stimulation (drTMS) has shown promising results as an add-on treatment for Parkinson’s disease (PD) but not for non-idiopathic Parkinson Syndromes (PS). We aimed to investigate the safety and feasibility of drTMS application in patients with different Parkinson Syndromes and medical refractory symptoms. Multifaceted real-world data (n = 21) were retrospectively analyzed regarding adverse effects as well as short-term effects of the drTMS treatment on patients’ self-rated symptom severity and motor, cognitive, and emotional functions. The drTMS treatment with H5 coil included a sequential 1 Hz primary motor cortex stimulation contralateral to the more-affected body side and a bilateral 10 Hz stimulation of the prefrontal cortex. Overall, drTMS could be safely administered to patients with different PSs and medical refractory symptoms, but large variation was apparent in the rate and severity ratings of the reported adverse event/adverse device effect. The treatment significantly decreased the subjective main symptom severity. This effect was more pronounced in older patients with PD. Furthermore, analysis showed an improvement in depression, but no effect could be established in terms of cognitive performance. drTMS can be safely administered to patients with PS and medical refractory symptoms and can decrease the subjective motor symptom severity and depression. Full article

(This article belongs to the Special Issue Advances in Parkinson’s Disease)

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6 pages, 1672 KiB

Open AccessCase Report

Hemispheric Asymmetry on the Electroencephalogram during General Anesthesia Responsive to Blood Pressure Manipulations

by Bryan T. Nycz, Andrew Chalhoub, Gaurav P. Patel, Cassandra E. Dean and Alexander Papangelou

Neurol. Int. 2022, 14(4), 1018-1023; https://doi.org/10.3390/neurolint14040081 - 7 Dec 2022

Cited by 1 | Viewed by 2224

Abstract

The electroencephalogram (EEG) has been extensively used to detect ischemia and the need for shunting during carotid endarterectomy. Limited literature exists using EEG data to detect ischemia in other surgeries. This case report depicts a 65-year-old man, with extensive vascular history including complete [...] Read more.

The electroencephalogram (EEG) has been extensively used to detect ischemia and the need for shunting during carotid endarterectomy. Limited literature exists using EEG data to detect ischemia in other surgeries. This case report depicts a 65-year-old man, with extensive vascular history including complete left carotid occlusion and severe right carotid stenosis, who presented for left first rib resection and left subclavian vein balloon angioplasty. Following induction of general anesthesia, frontal EEG (SedLine; Masimo Corporation, Irvine, CA, USA) demonstrated hemispheric asymmetry, which nearly resolved with vasoactive support. At three distinct periods, discordance reoccurred necessitating a higher mean arterial pressure threshold. This case demonstrates EEG patterns concerning for focal spectrographic ischemia and highlights the potential use of EEG signals to capture hypoperfusion and direct vasoactive therapy. Full article

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11 pages, 278 KiB

Open AccessArticle

Children, Adolescents, and Young Adults with Borderline Intellectual Functioning: Etiological, Neurophysiological, and Mri Findings in a Cohort of 651 Patients

by Heli Sätilä, Laura Mirjami Jolma and Mikko Koivu-Jolma

Neurol. Int. 2022, 14(4), 1007-1017; https://doi.org/10.3390/neurolint14040080 - 7 Dec 2022

Cited by 4 | Viewed by 2364

Abstract

This retrospective chart review study explored the etiology, use, and yield of the etiological investigations of 651 children and adolescents diagnosed with borderline intellectual functioning (BIF). Neurological, neurodevelopmental, or neuropsychiatric comorbidities were frequent, and in 23%, the BIF diagnosis evolved into an intellectual [...] Read more.

This retrospective chart review study explored the etiology, use, and yield of the etiological investigations of 651 children and adolescents diagnosed with borderline intellectual functioning (BIF). Neurological, neurodevelopmental, or neuropsychiatric comorbidities were frequent, and in 23%, the BIF diagnosis evolved into an intellectual disability (ID) by the time of discharge. A primary etiological cause was found in 37.6%, the most prevalent causes being pre- or perinatal conditions, genetic syndromes/chromosomal abnormalities, fetal exposure to maternal substance use, cerebral dysgenesis, and neurological diseases. In total, 79.1% of patients went through one or more investigations during their follow-up. The best etiologic yield leading to a diagnosis in this study population was with exome sequencing, a specific gene panel, microarrays, electroneuromyography, and brain magnetic resonance imaging (MRI). Etiological investigations were performed more frequently among those children receiving an ID diagnosis. Yet, there was no statistically significant difference in the proportion of abnormal findings between the BIF and ID groups. This may mean that the current strategy for determining the need for etiological investigations or current means to gain an etiology is still indecisive. Considering that BIF is defined to include individuals performing between normal cognitive functioning and mild ID, this implies that the prevalence would be anywhere between 7 and 14%. Thus, it could be argued whether in-depth etiological investigations may be justified in cases other than ID in this age group of children over five. With these children and adolescents, the clinicians have to discern between those with a normal variation and those having major difficulties in adaptive behavior affecting everyday life in order to specify and prescribe the rehabilitation or other measures needed. We advocate for a targeted etiological search after careful history-taking and neurological examination. National guidelines that take into account the severity of developmental delay are warranted. Full article

(This article belongs to the Special Issue Global Burden of Neurological Disorder)

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10 pages, 1016 KiB

Open AccessSystematic Review

Relevance of Fluorodopa PET Scan in Dopamine Responsive Dystonia and Juvenile Parkinsonism: A Systematic Review

by Juan A. Moncayo, Maite Vargas, Juan F. Ortiz, Pablo Granda, Alex S. Aguirre, Jennifer Argudo, Willians Tambo, Gabriela Garofalo, Christian John Capirig, Melisa German-Montenegro and Luis G. Rueda

Neurol. Int. 2022, 14(4), 997-1006; https://doi.org/10.3390/neurolint14040079 - 2 Dec 2022

Viewed by 2958

Abstract

Background: Dopamine Responsive Dystonia (DRD) and Juvenile Parkinsonism (JP) are two diseases commonly presenting with parkinsonian symptoms in young patients. Current clinical guidelines offer a diagnostic approach based on molecular analysis. However, developing countries have limitations in terms of accessibility to these tests. [...] Read more.

Background: Dopamine Responsive Dystonia (DRD) and Juvenile Parkinsonism (JP) are two diseases commonly presenting with parkinsonian symptoms in young patients. Current clinical guidelines offer a diagnostic approach based on molecular analysis. However, developing countries have limitations in terms of accessibility to these tests. We aimed to assess the utility of imaging equipment, usually more available worldwide, to help diagnose and improve patients’ quality of life with these diseases. Methods: We performed a systematic literature review in English using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) and meta-analysis of observational studies in epidemiology (MOOSE) protocols. We only used human clinical trials about dopamine responsive dystonia and juvenile parkinsonism patients in which a fluorodopa (FD) positron emission tomography (PET) scan was performed to identify its use in these diseases. Results: We included six studies that fulfilled our criteria. We found a clear pattern of decreased uptake in the putamen and caudate nucleus in JP cases. At the same time, the results in DRD were comparable to normal subjects, with only a slightly decreased marker uptake in the previously mentioned regions by the FD PET scan. Conclusions: We found a distinctive pattern for each of these diseases. Identifying these findings with FD PET scans can shorten the delay in making a definitive diagnosis when genetic testing is unavailable, a common scenario in developing countries. Full article

(This article belongs to the Collection Brain Health Initiative: Advocacy in Global Neurology)

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6 pages, 1007 KiB

Open AccessCase Report

Anti-MOG Positive Bilateral Optic Neuritis and Brainstem Encephalitis Secondary to COVID-19 Infection: A Case Report

by Zisis Tsouris, Antonios Provatas, Christos Bakirtzis, Athina-Maria Aloizou, Vasileios Siokas, Vana Tsimourtou, Nikolaos Grigoriadis, Georgios M. Hadjigeorgiou and Efthimios Dardiotis

Neurol. Int. 2022, 14(4), 991-996; https://doi.org/10.3390/neurolint14040078 - 30 Nov 2022

Cited by 5 | Viewed by 2610

Abstract

(1) Introduction: There have been numerous reports on the neuroinvasive competence of SARS-CoV-2. Here, we present a case with anti-MOG positive bilateral optic neuritis and brainstem encephalitis secondary to COVID-19 infection. Additionally, we present a review of the current literature regarding the manifestation [...] Read more.

(1) Introduction: There have been numerous reports on the neuroinvasive competence of SARS-CoV-2. Here, we present a case with anti-MOG positive bilateral optic neuritis and brainstem encephalitis secondary to COVID-19 infection. Additionally, we present a review of the current literature regarding the manifestation of anti-MOG positive optic neuritis as well as anti-MOG positive encephalitis after COVID-19 infection. (2) Case Report: A 59-year-old female patient, with a recent history of COVID-19 infection, presented a progressive reduction of visual acuity and bilateral retrobulbar pain for the last 20 days. An ophthalmological examination revealed a decreased visual acuity (counting fingers) and a bilateral papilledema. An MRI scan of the brain revealed a mild thickening of the bilateral optic nerves and high-intensity lesions in the medial and right lateral pons. A high titer of IgG and IgM antibodies against SARS-CoV-2 in serum and antibodies against myelin oligodendrocyte glycoprotein (anti-MOG) in serum and CSF were revealed. The diagnosis of anti-MOG brainstem encephalitis and optic neuritis was set. (3) Conclusions: The history of COVID-19 infection should raise awareness about these autoimmune and infection-triggered diseases, such as anti-MOG antibody disease. Full article

(This article belongs to the Collection Advances in Neurodegenerative Diseases)

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10 pages, 1870 KiB

Open AccessArticle

The Utility of Automated ASPECTS in Acute Ischemic Stroke for Intravenous Recombinant Tissue Plasminogen Activator (IV-rtPA) Therapy

by Soichiro Shibata, Kenzo Sakurai, Keiji Tachikawa, Riyoko Ko, Sakae Hino, Takayuki Fukano, Kenji Isahaya, Takafumi Haraguchi, Junji Yamauchi, Kenichiro Tanabe, Misako Nagasaka, Yuta Hagiwara, Takahiro Shimizu, Hisanao Akiyama, Yasuyuki Kobayashi, Yasuhiro Hasegawa and Yoshihisa Yamano

Neurol. Int. 2022, 14(4), 981-990; https://doi.org/10.3390/neurolint14040077 - 21 Nov 2022

Cited by 2 | Viewed by 2290

Abstract

Purpose: This study aimed to investigate the accuracy and clinical significance of an artificial intelligence (AI)-based automated Alberta Stroke Program Early Computed Tomography (ASPECT) scoring software of head CT for the indication of intravenous recombinant tissue plasminogen activator (rt-PA) therapy. Methods: This study [...] Read more.

Purpose: This study aimed to investigate the accuracy and clinical significance of an artificial intelligence (AI)-based automated Alberta Stroke Program Early Computed Tomography (ASPECT) scoring software of head CT for the indication of intravenous recombinant tissue plasminogen activator (rt-PA) therapy. Methods: This study included two populations of acute ischemic stroke: one comprised patients who had undergone head CT within 48 h of presentation (Population #1, n = 448), while the other included patients within 4.5 h from onset (Population #2, n = 132). The primary endpoint was the concordance rate of ASPECTS of the neurologists and AI software against the benchmark score. The secondary endpoints were to validate the accuracy of the neurologist and AI software in assessing the ability to rule out extensive infarction (ASPECTS of 0–5) in population #2. Results: The reading accuracy of AI software was comparable to that of the board-certified vascular neurologists. The detection rate of cardiogenic cerebral embolism was better than that of atherothrombotic cerebral infarction. By excluding extensive infarction, AI-software showed a higher specificity and equivalent sensitivity compared to those of experts. Conclusions: The AI software for ASPECTS showed convincing agreement with expert evaluation and would be supportive in determining the indications of intravenous rt-PA therapy. Full article

(This article belongs to the Special Issue Stroke: From Pathophysiology to Therapy)

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29 pages, 856 KiB

Open AccessSystematic Review

The Clinical Utility of Leukoaraiosis as a Prognostic Indicator in Ischemic Stroke Patients

by Foteini Christidi, Dimitrios Tsiptsios, Anastasia Sousanidou, Stefanos Karamanidis, Sofia Kitmeridou, Stella Karatzetzou, Souzana Aitsidou, Konstantinos Tsamakis, Evlampia A. Psatha, Efstratios Karavasilis, Christos Kokkotis, Nikolaos Aggelousis and Konstantinos Vadikolias

Neurol. Int. 2022, 14(4), 952-980; https://doi.org/10.3390/neurolint14040076 - 17 Nov 2022

Cited by 8 | Viewed by 2536

Abstract

Stroke constitutes a major cause of functional disability with increasing prevalence among adult individuals. Thus, it is of great importance for both clinicians and stroke survivors to be provided with a timely and accurate prognostication of functional outcome. A great number of biomarkers [...] Read more.

Stroke constitutes a major cause of functional disability with increasing prevalence among adult individuals. Thus, it is of great importance for both clinicians and stroke survivors to be provided with a timely and accurate prognostication of functional outcome. A great number of biomarkers capable of yielding useful information regarding stroke patients’ recovery propensity have been evaluated so far with leukoaraiosis being among them. Literature research of two databases (MEDLINE and Scopus) was conducted to identify all relevant studies published between 1 January 2012 and 25 June 2022 that dealt with the clinical utility of a current leukoaraiosis as a prognostic indicator following stroke. Only full-text articles published in English language were included. Forty-nine articles have been traced and are included in the present review. Our findings highlight the prognostic value of leukoaraiosis in an acute stroke setting. The assessment of leukoaraiosis with visual rating scales in CT/MRI imaging appears to be able to reliably provide important insight into the recovery potential of stroke survivors, thus significantly enhancing stroke management. Yielding additional information regarding both short- and long-term functional outcome, motor recovery capacity, hemorrhagic transformation, as well as early neurological deterioration following stroke, leukoaraiosis may serve as a valuable prognostic marker poststroke. Thus, leukoaraiosis represents a powerful prognostic tool, the clinical implementation of which is expected to significantly facilitate the individualized management of stroke patients. Full article

(This article belongs to the Special Issue Stroke: From Pathophysiology to Therapy)

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9 pages, 1694 KiB

Open AccessArticle

Humoral Response to SARS-CoV-2 Antigen in Patients Treated with Monoclonal Anti-CD20 Antibodies: It Is Not All about B Cell Recovery

by Julia Feige, Klaus Berek, Michael Seiberl, Patrick Hilpold, Wolfgang Hitzl, Franziska Di Pauli, Harald Hegen, Florian Deisenhammer, Eugen Trinka, Andrea Harrer, Peter Wipfler and Tobias Moser

Neurol. Int. 2022, 14(4), 943-951; https://doi.org/10.3390/neurolint14040075 - 16 Nov 2022

Cited by 1 | Viewed by 2046

Abstract

Anti-CD20 therapies decrease the humoral response to SARS-CoV-2 immunization. We aimed to determine the extent of the humoral response to SARS-CoV-2 antigens in correlation with peripheral B-cell dynamics among patients with central nervous system inflammatory disorders treated with anti-CD20 medications. We retrospectively included [...] Read more.

Anti-CD20 therapies decrease the humoral response to SARS-CoV-2 immunization. We aimed to determine the extent of the humoral response to SARS-CoV-2 antigens in correlation with peripheral B-cell dynamics among patients with central nervous system inflammatory disorders treated with anti-CD20 medications. We retrospectively included patients receiving anti-CD20 therapy after antigen contact who were divided into responders (>7 binding antibody units (BAU)/mL) and non-responders (<7 BAU/mL). In participants with first antigen contact prior to therapy, we investigated the recall response elicited once under treatment. We included 80 patients (responders n = 34, non-responders n = 37, recall cohort n = 9). The B-cell counts among responders were significantly higher compared to non-responders (mean 1012 cells/µL ± SD 105 vs. mean 17 cells/µL ± SD 47; p < 0.001). Despite very low B-cell counts (mean 9 cells/µL ± SD 20), humoral response was preserved among the recall cohort (mean 1653 BAU/mL ± SD 2250.1) and did not differ significantly from responders (mean 735 BAU/mL ± SD 1529.9; p = 0.14). Our data suggest that peripheral B cells are required to generate antibodies to neo-antigens but not for a recall response during anti-CD20 therapy. Evaluation of B-cell counts and pre-existing SARS-CoV-2 antibodies might serve as biomarkers for estimating the immune competence to mount a humoral response to SARS-CoV-2 antigens. Full article

(This article belongs to the Special Issue COVID-19, Neuroinflammation and Therapeutics)

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20 pages, 634 KiB

Open AccessSystematic Review

Elucidating the Role of Baseline Leukoaraiosis on Forecasting Clinical Outcome of Acute Ischemic Stroke Patients Undergoing Reperfusion Therapy

by Stella Karatzetzou, Dimitrios Tsiptsios, Anastasia Sousanidou, Foteini Christidi, Evlampia A. Psatha, Marilena Chatzaki, Sofia Kitmeridou, Erasmia Giannakou, Efstratios Karavasilis, Christos Kokkotis, Nikolaos Aggelousis and Konstantinos Vadikolias

Neurol. Int. 2022, 14(4), 923-942; https://doi.org/10.3390/neurolint14040074 - 10 Nov 2022

Cited by 5 | Viewed by 1912

Abstract

Stroke stands as a major cause of death and disability with increasing prevalence. The absence of clinical improvement after either intravenous thrombolysis (IVT) or mechanical thrombectomy (MT) represents a frequent concern in the setting of acute ischemic stroke (AIS). In an attempt to [...] Read more.

Stroke stands as a major cause of death and disability with increasing prevalence. The absence of clinical improvement after either intravenous thrombolysis (IVT) or mechanical thrombectomy (MT) represents a frequent concern in the setting of acute ischemic stroke (AIS). In an attempt to optimize overall stroke management, it is clinically valuable to provide important insight into functional outcomes after reperfusion therapy among patients presenting with AIS. The aim of the present review is to explore the predictive value of leukoaraiosis (LA) in terms of clinical response to revascularization poststroke. A literature research of two databases (MEDLINE and Scopus) was conducted in order to trace all relevant studies published between 1 January 2012 and 1 November 2022 that focused on the potential utility of LA severity regarding reperfusion status and clinical outcome after revascularization. A total of 37 articles have been traced and included in this review. LA burden assessment is indicative of functional outcome post-intervention and may be associated with hemorrhagic events’ incidence among stroke individuals. Nevertheless, LA may not solely guide decision-making about treatment strategy poststroke. Overall, the evaluation of LA upon admission seems to have interesting prognostic potential and may substantially enhance individualized stroke care. Full article

(This article belongs to the Collection Biomarkers in Stroke Prognosis)

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20 pages, 1962 KiB

Open AccessArticle

Association of Lesion Topography with Functional Outcomes in Acute Ischemic Stroke Patients Considered for, or Receiving, Reperfusion Therapy: A Meta-Analysis

by Shuyue Chen, Kevin J. Spring, Murray C. Killingsworth, Zeljka Calic, Roy G. Beran and Sonu M. M. Bhaskar

Neurol. Int. 2022, 14(4), 903-922; https://doi.org/10.3390/neurolint14040073 - 7 Nov 2022

Viewed by 2351

Abstract

Background: The impact of lesion topography (LT), characterised by the Alberta Stroke Programme Early CT Score (ASPECTS), on outcomes after reperfusion therapy in acute ischemic stroke (AIS) is poorly elucidated. We investigated the prognostic accuracy of ASPECTS-based LT assessment and its association with [...] Read more.

Background: The impact of lesion topography (LT), characterised by the Alberta Stroke Programme Early CT Score (ASPECTS), on outcomes after reperfusion therapy in acute ischemic stroke (AIS) is poorly elucidated. We investigated the prognostic accuracy of ASPECTS-based LT assessment and its association with clinical outcomes in AIS patients considered for reperfusion therapy or receiving intravenous thrombolysis (IVT), endovascular thrombectomy (EVT), or none or both. Methods: Studies were identified from PubMed with additional studies added from Google Scholar. The prevalence of individual ASPECTS regions will also be determined. The association of individual ASPECTS regions with the functional outcome at 90 days will be assessed using random-effects modelling for various cut-offs, such as 6, 7 and 8. The association of continuous ASPECTS with the functional outcome at 90 days will also be undertaken. Forest plots of odds ratios (ORs) will be generated. Results: A total of 25 studies have been included in the final analysis, encompassing 11,404 patients. Pooled estimates indicate that the highest prevalence rates were in cases involving the insula and lentiform nucleus. Subgroup analysis for ASPECTS < 6 (OR 6.10; 95% CI 2.50–14.90; p < 0.0001), ASPECTS < 7 (OR 4.58; 95% CI 1.18–17.86; p < 0.0001) and ASPECTS < 8 (OR 2.26; 95% CI 1.32–3.89; p < 0.0001) revealed a significant association with poor functional outcome at 90 days. Decreasing ASPECTS significantly increased the odds of poor functional outcomes at 90 days (SMD −1.15; 95% CI −1.77–−0.52; p < 0.0001). Conclusions: Our meta-analysis demonstrates that decreasing ASPECTS is significantly associated with poor functional outcomes. Individual ASPECTS regions associated with the highest odds of poor functional outcomes were identified. Future studies on the association of LT and clinical outcomes specific to EVT are required. Full article

(This article belongs to the Special Issue Stroke: From Pathophysiology to Therapy)

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9 pages, 11203 KiB

Open AccessArticle

Anatomical Variations of the Sciatic Nerve Exit from the Pelvis and Its Relationship with the Piriformis Muscle: A Cadaveric Study

by Juan Pablo Reynoso, Manuel De Jesus Encarnacion, Renat Nurmukhametov, Dmitry Melchenko, Ibrahim E. Efe, Evgeniy Goncharov, Angel Alfonso Taveras, Issael Jesus Ramirez Pena and Nicola Montemurro

Neurol. Int. 2022, 14(4), 894-902; https://doi.org/10.3390/neurolint14040072 - 31 Oct 2022

Cited by 11 | Viewed by 5851

Abstract

Background: The sciatic nerve (SN) is the widest nerve of the human body that exits the pelvis through the greater sciatic foramen, usually below the piriformis muscle (PM), and descends between the greater trochanter of the femur and ischial tuberosity of the pelvis [...] Read more.

Background: The sciatic nerve (SN) is the widest nerve of the human body that exits the pelvis through the greater sciatic foramen, usually below the piriformis muscle (PM), and descends between the greater trochanter of the femur and ischial tuberosity of the pelvis to the knee. The aim of this paper is to examine and identify the SN variations in relation to the PM, its prevalence, pattern, and course. Methods: A prospective-descriptive cross-sectional study was carried out to determine the frequency of anatomical variations in the exit of the SN in relation with the PM in 20 anatomical bodies (corpses) of both genders, in equal numbers. Results: The dissection of 40 SNs in corpses of both sexes in equal numbers showed that the SN exited inferior to the PM in 37 lower limbs (92.5%); between the fascicles of the PM and inferior to the PM in two lower limbs (5%); and in one thigh, between the fascicles of the PM and superior to the PM (2.5%). Our study reported that the SN divides in its terminal branches more commonly in the proximal part of the popliteal fossa in 55% of cases, in the gluteal region in 35% of cases, and in the middle third of the thigh in 10% of cases. Conclusions: Anatomical variations of the SN in relation to the PM are challenging for the diagnostic and therapeutic procedure in many clinical and surgical cases. Rapid recognition of the SN changes makes surgical approaches more accurate and effective. Our study confirmed that the SN exits the pelvis most commonly below the PM, although some anatomical variations may occur. Full article

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10 pages, 1675 KiB

Open AccessReview

Lights on for Autism: Exploring Photobiomodulation as an Effective Therapeutic Option

by Catherine Hamilton, Ann Liebert, Vincent Pang, Pierre Magistretti and John Mitrofanis

Neurol. Int. 2022, 14(4), 884-893; https://doi.org/10.3390/neurolint14040071 - 27 Oct 2022

Cited by 6 | Viewed by 8839

Abstract

Autism is a neurodevelopmental condition that starts in childhood and continues into adulthood. The core characteristics include difficulties with social interaction and communication, together with restricted and repetitive behaviours. There are a number of key abnormalities of brain structure and function that trigger [...] Read more.

Autism is a neurodevelopmental condition that starts in childhood and continues into adulthood. The core characteristics include difficulties with social interaction and communication, together with restricted and repetitive behaviours. There are a number of key abnormalities of brain structure and function that trigger these behavioural patterns, including an imbalance of functional connectivity and synaptic transmission, neuronal death, gliosis and inflammation. In addition, autism has been linked to alterations in the gut microbiome. Unfortunately, as it stands, there are few treatment options available for patients. In this mini-review, we consider the effectiveness of a potential new treatment for autism, known as photobiomodulation, the therapeutic use of red to near infrared light on body tissues. This treatment has been shown in a range of pathological conditions-to improve the key changes that characterise autism, including the functional connectivity and survival patterns of neurones, the patterns of gliosis and inflammation and the composition of the microbiome. We highlight the idea that photobiomodulation may form an ideal treatment option for autism, one that is certainly worthy of further investigation. Full article

(This article belongs to the Collection Advances in Neurodegenerative Diseases)

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9 pages, 1338 KiB

Open AccessArticle

Twelve-Month Results from a Prospective Clinical Study Evaluating the Efficacy and Safety of Cellular Bone Allograft in Subjects Undergoing Lumbar Spinal Fusion

by Joshua Wind, Daniel Park, Todd Lansford, Pierce Nunley, Timothy Peppers, Anthony Russo, Hamid Hassanzadeh, Jonathan N. Sembrano, Jung Yoo and Jonathan Sales

Neurol. Int. 2022, 14(4), 875-883; https://doi.org/10.3390/neurolint14040070 - 26 Oct 2022

Cited by 8 | Viewed by 4114

Abstract

Background: While autologous bone grafts remain the gold standard for spinal fusion procedures, harvesting autologous bone is associated with significant complications, including donor site infection, hematomas, increased operative time, and prolonged pain. Cellular bone allograft (CBA) presents an alternative to autologous bone harvesting, [...] Read more.

Background: While autologous bone grafts remain the gold standard for spinal fusion procedures, harvesting autologous bone is associated with significant complications, including donor site infection, hematomas, increased operative time, and prolonged pain. Cellular bone allograft (CBA) presents an alternative to autologous bone harvesting, with a favorable efficacy and safety profile. The current study further investigates CBA as an adjunct to lumbar spinal fusion procedures. Methods: A prospective, multicenter, open-label clinical study was conducted in subjects undergoing lumbar spinal fusion with CBA (NCT 02969616). Radiographic fusion status was assessed by an independent review of dynamic radiographs and CT scans. Clinical outcome measures included the Oswestry Disability Index (ODI) and visual analogue scale (VAS) for back and leg pain. Adverse-event reporting was conducted throughout 12 months of follow-up. Available subject data at 12 months were analyzed. Results: A total of 274 subjects were enrolled into the study, with available data from 201 subjects (73.3%) who completed 12 months of postoperative radiographic and clinical evaluation at the time of analysis. Subjects had a mean age of 60.2 ± 11.5 years. A higher number of women (n = 124, 61.7%) than men (n = 77, 38.3%) were enrolled, with a collective mean BMI of 30.6 + 6.5 kg/m² (range 18.0–51.4). At month 12, successful fusion was achieved in 90.5% of subjects. A significant (p < 0.001) improvement in ODI, VAS-back, and VAS-leg clinical outcomes was also observed compared to baseline scores. One adverse event related to CBA (postoperative radiculopathy) was reported, with surgical exploration demonstrating interbody extrusion of graft material. This subject reported successful fusion at month 12. Conclusions: CBA represents a viable substitute for harvesting of autograft alone with a high rate of successful fusion and significant improvements in subject-reported outcomes, such as pain and disability. Positive benefit was observed in subjects reporting single and multiple risk factors for pseudoarthrosis. Full article

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34 pages, 2644 KiB

Open AccessReview

Diffusion Tensor Imaging as a Prognostic Tool for Recovery in Acute and Hyperacute Stroke

by Foteini Christidi, Dimitrios Tsiptsios, Aggeliki Fotiadou, Sofia Kitmeridou, Stella Karatzetzou, Konstantinos Tsamakis, Anastasia Sousanidou, Evlampia A. Psatha, Efstratios Karavasilis, Ioannis Seimenis, Christos Kokkotis, Nikolaos Aggelousis and Konstantinos Vadikolias

Neurol. Int. 2022, 14(4), 841-874; https://doi.org/10.3390/neurolint14040069 - 21 Oct 2022

Cited by 12 | Viewed by 4311

Abstract

Stroke represents a major cause of mortality and long-term disability among adult populations, leaving a devastating socioeconomic impact globally. Clinical manifestation of stroke is characterized by great diversity, ranging from minor disability to considerable neurological impairment interfering with activities of daily living and [...] Read more.

Stroke represents a major cause of mortality and long-term disability among adult populations, leaving a devastating socioeconomic impact globally. Clinical manifestation of stroke is characterized by great diversity, ranging from minor disability to considerable neurological impairment interfering with activities of daily living and even death. Prognostic ambiguity has stimulated the interest for implementing stroke recovery biomarkers, including those provided by structural neuroimaging techniques, i.e., diffusion tensor imaging (DTI) and tractography for the study of white matter (WM) integrity. Considering the necessity of prompt and accurate prognosis in stroke survivors along with the potential capacity of DTI as a relevant imaging biomarker, the purpose of our study was to review the pertinent literature published within the last decade regarding DTI as a prognostic tool for recovery in acute and hyperacute stroke. We conducted a thorough literature search in two databases (MEDLINE and Science Direct) in order to trace all relevant studies published between 1 January 2012 and 16 March 2022 using predefined terms as key words. Only full-text human studies published in the English language were included. Forty-four studies were identified and are included in this review. We present main findings and by describing several methodological issues, we highlight shortcomings and gaps in the current literature so that research priorities for future research can be outlined. Our review suggests that DTI can track longitudinal changes and identify prognostic correlates in acute and hyperacute stroke patients. Full article

(This article belongs to the Special Issue Stroke: From Pathophysiology to Therapy)

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2 pages, 195 KiB

Open AccessComment

Comment on Rauchman et al. Mild-to-Moderate Traumatic Brain Injury: A Review with Focus on the Visual System. Neurol. Int. 2022, 14, 453–470

by Nir Erdinest and Naomi London

Neurol. Int. 2022, 14(4), 839-840; https://doi.org/10.3390/neurolint14040068 - 21 Oct 2022

Viewed by 1445

Abstract

This letter is regarding the article, “Mild-to-Moderate Traumatic Brain Injury: A Review with Focus on the Visual System” [...] Full article

15 pages, 1074 KiB

Open AccessArticle

Where Am I? Searching for the Tangle in the Developmental Topographical Disorientation

by Laura Piccardi, Vincenza Cofini, Massimiliano Palmiero, Paola Verde, Maddalena Boccia, Liana Palermo, Cecilia Guariglia and Raffaella Nori

Neurol. Int. 2022, 14(4), 824-838; https://doi.org/10.3390/neurolint14040067 - 20 Oct 2022

Cited by 2 | Viewed by 2442

Abstract

The Developmental Topographical Disorientation (DTD) is a pathological condition that impairs an individual’s ability to orient in space, even in the most familiar environments. It is a lifelong selective condition in individuals without brain damage or without impaired general cognitive functions. Here, we [...] Read more.

The Developmental Topographical Disorientation (DTD) is a pathological condition that impairs an individual’s ability to orient in space, even in the most familiar environments. It is a lifelong selective condition in individuals without brain damage or without impaired general cognitive functions. Here, we aimed at characterizing 54 individuals with DTD identified in a previous study, aged between 18 and 35 years and assessed through a 4-year-long online survey. To this purpose, we compared them with 54 matched healthy participants. We described the demographics, sense of direction, town knowledge, navigational strategies, left-right confusion as well as agnosic disorders (for landmarks, faces and objects). This novel study attempts to characterize the phenotype of DTD, providing an important contribution to the worldwide definition of a condition that was first described only 13 years ago, but which, considering the growing number of cases complaining of the disorder, deserves continuous and increasing attention. Full article

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20 pages, 5820 KiB

Open AccessArticle

Radix Glycyrrhizae Preparata Induces Cell Cycle Arrest and Induced Caspase-Dependent Apoptosis in Glioblastoma Multiforme

by Tsung-Ying Lin, Tung-Hsuan Wu, Rong-Dar Tzou, Yi-Chiang Hsu, Kuan-Ting Lee and Tai-Hsin Tsai

Neurol. Int. 2022, 14(4), 804-823; https://doi.org/10.3390/neurolint14040066 - 13 Oct 2022

Cited by 3 | Viewed by 2531

Abstract

Glioblastoma multiforme (GBM) is a highly aggressive and devastating brain tumor characterized by poor prognosis and high rates of recurrence. Despite advances in multidisciplinary treatment, GBM constinues to have a poor overall survival. The Radix Glycyrrhizae Preparata (RGP) has been reported to possess [...] Read more.

Glioblastoma multiforme (GBM) is a highly aggressive and devastating brain tumor characterized by poor prognosis and high rates of recurrence. Despite advances in multidisciplinary treatment, GBM constinues to have a poor overall survival. The Radix Glycyrrhizae Preparata (RGP) has been reported to possess anti-allergic, neuroprotective, antioxidative, and anti-inflammatory activities. However, it not clear what effect it may have on tumorigenesis in GBM. This study demonstrated that RGP reduced glioma cell viability and attenuated glioma cell locomotion in GBM8401 and U87MG cells. RGP treated cells had significant increase in the percentage of apoptotic cells and rise in the percentage of caspase-3 activity. In addition, the results of study’s cell cycle analysis also showed that RGP arrested glioma cells at G₂/M phase and Cell failure pass the G2 checkpoint by RGP treatment in GBM8401 Cells. Based on the above results, it seems to imply that RGP activated DNA damage checkpoint system and cell cycle regulators and induce apoptosis in established GBM cells. In conclusion, RGP can inhibit proliferation, cell locomotion, cell cycle progression and induce apoptosis in GBM cells in vitro. Full article

(This article belongs to the Topic Novel Diagnostic and Therapeutic Strategies in Gliomas)

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20 pages, 685 KiB

Open AccessEditor’s ChoiceReview

Stroke and Emerging Blood Biomarkers: A Clinical Prospective

by Aimilios Gkantzios, Dimitrios Tsiptsios, Stella Karatzetzou, Sofia Kitmeridou, Vaia Karapepera, Erasmia Giannakou, Penelope Vlotinou, Nikolaos Aggelousis and Konstantinos Vadikolias

Neurol. Int. 2022, 14(4), 784-803; https://doi.org/10.3390/neurolint14040065 - 22 Sep 2022

Cited by 24 | Viewed by 5454

Abstract

Stroke constitutes the primary source of adult functional disability, exhibiting a paramount socioeconomic burden. Thus, it is of great importance that the prediction of stroke outcome be both prompt and accurate. Although modern neuroimaging and neurophysiological techniques are accessible, easily available blood biomarkers [...] Read more.

Stroke constitutes the primary source of adult functional disability, exhibiting a paramount socioeconomic burden. Thus, it is of great importance that the prediction of stroke outcome be both prompt and accurate. Although modern neuroimaging and neurophysiological techniques are accessible, easily available blood biomarkers reflecting underlying stroke-related pathophysiological processes, including glial and/or neuronal death, neuroendocrine responses, inflammation, increased oxidative stress, blood–brain barrier disruption, endothelial dysfunction, and hemostasis, are required in order to facilitate stroke prognosis. A literature search of two databases (MEDLINE and Science Direct) was conducted in order to trace all relevant studies published between 1 January 2010 and 31 December 2021 that focused on the clinical utility of brain natriuretic peptide, glial fibrillary acidic protein, the red cell distribution width, the neutrophil-to-lymphocyte ratio, matrix metalloproteinase-9, and aquaporin-4 as prognostic tools in stroke survivors. Only full-text articles published in English were included. Twenty-eight articles were identified and are included in this review. All studied blood-derived biomarkers proved to be valuable prognostic tools poststroke, the clinical implementation of which may accurately predict the survivors’ functional outcomes, thus significantly enhancing the rehabilitation efficiency of stroke patients. Along with already utilized clinical, neurophysiological, and neuroimaging biomarkers, a blood-derived multi-biomarker panel is proposed as a reasonable approach to enhance the predictive power of stroke prognostic models. Full article

(This article belongs to the Special Issue Stroke: From Pathophysiology to Therapy)

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13 pages, 900 KiB

Open AccessArticle

Distortions in Spatial Mental Representation Affect Sketch Maps in Young Adults

by Antonella Lopez and Andrea Bosco

Neurol. Int. 2022, 14(4), 771-783; https://doi.org/10.3390/neurolint14040064 - 21 Sep 2022

Cited by 3 | Viewed by 1953

Abstract

Humans tend to misrepresent spatial information which leads to systematic errors due to distorted organizational processes regarding metric and positional judgments. This study is aimed at analyzing metric and positional distortions in cognitive maps by using external representations, namely sketch maps, in two [...] Read more.

Humans tend to misrepresent spatial information which leads to systematic errors due to distorted organizational processes regarding metric and positional judgments. This study is aimed at analyzing metric and positional distortions in cognitive maps by using external representations, namely sketch maps, in two experiments with young participants. In the first experiment, we use the sketching area of Northern Europe. In the second experiment, the University campus area was used. The first aim was to test the hypothesis that the presence of the sea between the triplet of landmarks generates an overestimation of the distances between them in the case of Northern Europe; and to test the hypothesis that the number of turns in a route influences the overestimation of the distance between landmarks in the case of the campus area. The second aim was to investigate alignment and rotation errors using the same maps. Concerning metric errors, the results showed the overestimation of distances with a geographical gap between the cities (the sea in the Northern European Area), and those with more turns between landmarks (the campus area). The results concerning rotations and alignments were in line with the previous research about positional errors. The present study extended findings on distortions in spatial mental representation as emerging from verbal judgments, to sketch maps: direct visuospatial external representations eluding the conversion into verbal coding of spatial information. The presence of distortions in cognitive maps could be considered the consequence of the encoding of spatial information. Full article

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23 pages, 5602 KiB

Open AccessArticle

Is Composition of Brain Clot Retrieved by Mechanical Thrombectomy Associated with Stroke Aetiology and Clinical Outcomes in Acute Ischemic Stroke?—A Systematic Review and Meta-Analysis

by Joanna Huang, Murray C. Killingsworth and Sonu M. M. Bhaskar

Neurol. Int. 2022, 14(4), 748-770; https://doi.org/10.3390/neurolint14040063 - 20 Sep 2022

Cited by 12 | Viewed by 3626

Abstract

Background: Brain clots retrieved following endovascular thrombectomy in acute ischemic stroke patients may offer unique opportunities to characterise stroke aetiology and aid stroke decision-making in select groups of patients. However, the evidence around the putative association of clot morphology with stroke aetiology is [...] Read more.

Background: Brain clots retrieved following endovascular thrombectomy in acute ischemic stroke patients may offer unique opportunities to characterise stroke aetiology and aid stroke decision-making in select groups of patients. However, the evidence around the putative association of clot morphology with stroke aetiology is limited and remains inconclusive. This study aims to perform a systematic review and meta-analysis to delineate the association of brain clot composition with stroke aetiology and post-reperfusion outcomes in patients receiving endovascular thrombectomy. Methods: The authors conducted a systematic literature review and meta-analysis by extracting data from several research databases (MEDLINE/PubMed, Cochrane, and Google Scholar) published since 2010. We used appropriate key search terms to identify clinical studies concerning stroke thrombus composition, aetiology, and clinical outcomes, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: The authors identified 30 articles reporting on the relationship between stroke thrombus composition or morphology and aetiology, imaging, or clinical outcomes, of which 21 were included in the meta-analysis. The study found that strokes of cardioembolic origin (SMD = 0.388; 95% CI, 0.032–0.745) and cryptogenic origin (SMD = 0.468; 95% CI, 0.172–0.765) had significantly higher fibrin content than strokes of non-cardioembolic origin. Large artery atherosclerosis strokes had significantly lower fibrin content than cardioembolic (SMD = 0.552; 95% CI, 0.099–1.004) or cryptogenic (SMD = 0.455; 95% CI, 0.137–0.774) strokes. Greater red blood cell content was also significantly associated with a thrombolysis in cerebral infarction score of 2b–3 (SMD = 0.450; 95% CI, 0.177–0.722), and a positive hyperdense middle cerebral artery sign (SMD = 0.827; 95% CI, 0.472–1.183). No significant associations were found between red blood cell, platelet, or white blood cell content and aetiology, or between clot composition and bridging thrombolysis. Conclusions: This meta-analysis found that fibrin composition is significantly higher in strokes of cardioembolic and cryptogenic origin, and that red blood cell content is positively associated with the hyperdense middle cerebral artery sign and better reperfusion outcomes. Important advances to stroke clinical workup can be derived from these findings, in which many aspects of stroke workflow remain to be optimised. As data are still limited in terms of the association of various thrombus components with stroke aetiology as well as a standardised method of analysis, further studies are required to validate these findings to guide their use in clinical decision-making. Full article

(This article belongs to the Special Issue Stroke: From Pathophysiology to Therapy)

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Neurol. Int., Volume 14, Issue 4 (December 2022) – 23 articles

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