Pub Date : 2024-06-11DOI: 10.3390/neurolint16030049
Sosuke Yagishita, Megumi Shibata, Akiko Furuno, S. Wakatsuki, T. Araki
The tau protein is a microtubule-associated protein that promotes microtubule stabilization. The phosphorylation of the tau protein has been linked to its dissociation from microtubules. Here, we examined the relationship between neuronal depolarization activity and tau protein phosphorylation by employing model systems in culture as well as in vivo. The KCl-evoked depolarization of cultured neurons has often been used to investigate the effects of neuronal activity. We found dephosphorylation at AT8 sites (S202, T205), T212, AT180 sites (T231, S235), and S396 in KCl-simulated cultured neurons. We also found that the KCl-induced tau protein dephosphorylation increases the level of the tau protein fractionated with stable microtubules. In an in vivo experiment, we demonstrated that the exposure of mice to a new environment activates protein phosphatase 1 in the mouse hippocampus and induces tau protein dephosphorylation. We also found an increased amount of the tau protein in a stable microtubule fraction, suggesting that the dephosphorylation of the tau protein may lead to its increased microtubule association in vivo. These results suggest that the association of microtubules with tau proteins may be regulated by the tau protein phosphorylation status affected by neuronal electrical activity.
tau 蛋白是一种促进微管稳定的微管相关蛋白。tau 蛋白的磷酸化与其与微管的分离有关。在这里，我们利用培养和体内模型系统研究了神经元去极化活动与 tau 蛋白磷酸化之间的关系。KCl诱发的培养神经元去极化经常被用来研究神经元活动的影响。我们发现，在 KCl 模拟的培养神经元中，AT8 位点（S202、T205）、T212、AT180 位点（T231、S235）和 S396 均存在去磷酸化现象。我们还发现，KCl 诱导的 tau 蛋白去磷酸化增加了与稳定微管分馏在一起的 tau 蛋白的水平。在一项体内实验中，我们证实小鼠暴露于新环境会激活小鼠海马中的蛋白磷酸酶1，并诱导tau蛋白去磷酸化。我们还发现，在稳定的微管部分中，tau 蛋白的数量有所增加，这表明 tau 蛋白的去磷酸化可能导致其在体内与微管的结合增加。这些结果表明，微管与 tau 蛋白的结合可能受神经元电活动影响的 tau 蛋白磷酸化状态的调节。
{"title":"Neuronal Excitation Induces Tau Protein Dephosphorylation via Protein Phosphatase 1 Activation to Promote Its Binding with Stable Microtubules","authors":"Sosuke Yagishita, Megumi Shibata, Akiko Furuno, S. Wakatsuki, T. Araki","doi":"10.3390/neurolint16030049","DOIUrl":"https://doi.org/10.3390/neurolint16030049","url":null,"abstract":"The tau protein is a microtubule-associated protein that promotes microtubule stabilization. The phosphorylation of the tau protein has been linked to its dissociation from microtubules. Here, we examined the relationship between neuronal depolarization activity and tau protein phosphorylation by employing model systems in culture as well as in vivo. The KCl-evoked depolarization of cultured neurons has often been used to investigate the effects of neuronal activity. We found dephosphorylation at AT8 sites (S202, T205), T212, AT180 sites (T231, S235), and S396 in KCl-simulated cultured neurons. We also found that the KCl-induced tau protein dephosphorylation increases the level of the tau protein fractionated with stable microtubules. In an in vivo experiment, we demonstrated that the exposure of mice to a new environment activates protein phosphatase 1 in the mouse hippocampus and induces tau protein dephosphorylation. We also found an increased amount of the tau protein in a stable microtubule fraction, suggesting that the dephosphorylation of the tau protein may lead to its increased microtubule association in vivo. These results suggest that the association of microtubules with tau proteins may be regulated by the tau protein phosphorylation status affected by neuronal electrical activity.","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141358958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The combined use of lasmiditan and triptan is unexplored in medical literature. This study aimed to investigate whether the intake of lasmiditan following triptan improves migraine pain. Following triptan intake, if headache relief was less than 50% at 1 h, patients took 50 mg of lasmiditan within 2 h of migraine onset. Patients recorded headache intensity and adverse events (AEs) caused by lasmiditan at 1, 2, and 4 h after the intake of an additional 50 mg of lasmiditan. A significant reduction in pain scale was observed post 50 mg lasmiditan intake (p < 0.001, t-test). Pain relief was reported for 32 migraine attacks (80%) at 1 h after additional lasmiditan intake. Although AEs were observed in 63% of the patients who took an additional lasmiditan, most were mild and resolved 1 h after lasmiditan intake. Our study revealed the significant headache relief provided by an additional lasmiditan for patients who did not achieve satisfactory results following initial triptan intake for treating migraine. The AEs associated with this treatment strategy were mild and lasted for a short time. This study suggested that the combination of triptan and lasmiditan is promising for the treatment of migraine and should be studied in a randomized placebo-controlled trial.
{"title":"Efficacy of Lasmiditan as a Secondary Treatment for Migraine Attacks after Unsuccessful Treatment with a Triptan","authors":"Yasushi Shibata, Hiroshige Sato, Akiko Sato, Yoichi Harada","doi":"10.3390/neurolint16030048","DOIUrl":"https://doi.org/10.3390/neurolint16030048","url":null,"abstract":"The combined use of lasmiditan and triptan is unexplored in medical literature. This study aimed to investigate whether the intake of lasmiditan following triptan improves migraine pain. Following triptan intake, if headache relief was less than 50% at 1 h, patients took 50 mg of lasmiditan within 2 h of migraine onset. Patients recorded headache intensity and adverse events (AEs) caused by lasmiditan at 1, 2, and 4 h after the intake of an additional 50 mg of lasmiditan. A significant reduction in pain scale was observed post 50 mg lasmiditan intake (p < 0.001, t-test). Pain relief was reported for 32 migraine attacks (80%) at 1 h after additional lasmiditan intake. Although AEs were observed in 63% of the patients who took an additional lasmiditan, most were mild and resolved 1 h after lasmiditan intake. Our study revealed the significant headache relief provided by an additional lasmiditan for patients who did not achieve satisfactory results following initial triptan intake for treating migraine. The AEs associated with this treatment strategy were mild and lasted for a short time. This study suggested that the combination of triptan and lasmiditan is promising for the treatment of migraine and should be studied in a randomized placebo-controlled trial.","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141371007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-04DOI: 10.3390/neurolint16030047
Asma AlTawari, Mohammad Zakaria, W. Kamel, Nayera Shaalan, Gamal Ahmed Ismail Elghazawi, Mohamed Esmat Anwar Ali, Dalia Salota, Amr Attia, Ehab Elsayed Ali Elanay, Osama Shalaby, Fatema Alqallaf, Vesna Mitic, Laila Bastaki
Spinal muscular atrophy is a neuromuscular genetic condition associated with progressive muscle weakness and atrophy. Nusinersen is an antisense oligonucleotide therapy approved for the treatment of 5q spinal muscular atrophy in pediatric and adult patients. The objective of this clinical case series is to describe the efficacy and safety of nusinersen in treating spinal muscular atrophy in 20 pediatric and 18 adult patients across six treatment centers in Kuwait. Functional motor assessments (Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders, Hammersmith Functional Motor Scale Expanded, and Revised Upper Limb Module) were used to assess changes in motor function following nusinersen treatment. The safety assessment involved clinical monitoring of adverse events. The results demonstrate clinically meaningful or considerable improvement in motor performance for nearly all patients, lasting over 4 years in some cases. A total of 70% of patients in the pediatric cohort and 72% of patients in the adult cohort achieved a clinically meaningful improvement in motor function following nusinersen treatment. Additionally, nusinersen was well-tolerated in both cohorts. These findings add to the growing body of evidence relating to the clinical efficacy and safety of nusinersen.
{"title":"Nusinersen Treatment for Spinal Muscular Atrophy: Retrospective Multicenter Study of Pediatric and Adult Patients in Kuwait","authors":"Asma AlTawari, Mohammad Zakaria, W. Kamel, Nayera Shaalan, Gamal Ahmed Ismail Elghazawi, Mohamed Esmat Anwar Ali, Dalia Salota, Amr Attia, Ehab Elsayed Ali Elanay, Osama Shalaby, Fatema Alqallaf, Vesna Mitic, Laila Bastaki","doi":"10.3390/neurolint16030047","DOIUrl":"https://doi.org/10.3390/neurolint16030047","url":null,"abstract":"Spinal muscular atrophy is a neuromuscular genetic condition associated with progressive muscle weakness and atrophy. Nusinersen is an antisense oligonucleotide therapy approved for the treatment of 5q spinal muscular atrophy in pediatric and adult patients. The objective of this clinical case series is to describe the efficacy and safety of nusinersen in treating spinal muscular atrophy in 20 pediatric and 18 adult patients across six treatment centers in Kuwait. Functional motor assessments (Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders, Hammersmith Functional Motor Scale Expanded, and Revised Upper Limb Module) were used to assess changes in motor function following nusinersen treatment. The safety assessment involved clinical monitoring of adverse events. The results demonstrate clinically meaningful or considerable improvement in motor performance for nearly all patients, lasting over 4 years in some cases. A total of 70% of patients in the pediatric cohort and 72% of patients in the adult cohort achieved a clinically meaningful improvement in motor function following nusinersen treatment. Additionally, nusinersen was well-tolerated in both cohorts. These findings add to the growing body of evidence relating to the clinical efficacy and safety of nusinersen.","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141267336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-02DOI: 10.3390/neurolint16030046
Sara Sablić, Krešimir Dolić, Danijela Budimir Mršić, Mate Čičmir-Vestić, A. Matana, Sanja Lovrić Kojundžić, Maja Marinović Guić
The collateral system is a compensatory mechanism activated in the acute phase of an ischemic stroke. It increases brain perfusion to the hypoperfused area. Arteries of the Willis’ circle supply antegrade blood flow, while pial (leptomeningeal) arteries direct blood via retrograde flow. The aim of our retrospective study was to investigate the relationship between both collateral systems, computed tomography perfusion (CTP) values, and functional outcomes in acute stroke patients. Overall, 158 patients with anterior circulation stroke who underwent mechanical thrombectomy were included in the study. We analyzed the presence of communicating arteries and leptomeningeal arteries on computed tomography angiography. Patients were divided into three groups according to their collateral status. The main outcomes were the rate of functional independence 3 months after stroke (modified Rankin scale score, mRS) and mortality rate. Our study suggests that the collateral status, as indicated by the three groups (unfavorable, intermediate, and favorable), is linked to CT perfusion parameters, potential recuperation ratio, and stroke outcomes. Patients with favorable collateral status exhibited smaller core infarct and penumbra volumes, higher mismatch ratios, better potential for recuperation, and improved functional outcomes compared to patients with unfavorable or intermediate collateral status.
{"title":"Communicating Arteries and Leptomeningeal Collaterals: A Synergistic but Independent Effect on Patient Outcomes after Stroke","authors":"Sara Sablić, Krešimir Dolić, Danijela Budimir Mršić, Mate Čičmir-Vestić, A. Matana, Sanja Lovrić Kojundžić, Maja Marinović Guić","doi":"10.3390/neurolint16030046","DOIUrl":"https://doi.org/10.3390/neurolint16030046","url":null,"abstract":"The collateral system is a compensatory mechanism activated in the acute phase of an ischemic stroke. It increases brain perfusion to the hypoperfused area. Arteries of the Willis’ circle supply antegrade blood flow, while pial (leptomeningeal) arteries direct blood via retrograde flow. The aim of our retrospective study was to investigate the relationship between both collateral systems, computed tomography perfusion (CTP) values, and functional outcomes in acute stroke patients. Overall, 158 patients with anterior circulation stroke who underwent mechanical thrombectomy were included in the study. We analyzed the presence of communicating arteries and leptomeningeal arteries on computed tomography angiography. Patients were divided into three groups according to their collateral status. The main outcomes were the rate of functional independence 3 months after stroke (modified Rankin scale score, mRS) and mortality rate. Our study suggests that the collateral status, as indicated by the three groups (unfavorable, intermediate, and favorable), is linked to CT perfusion parameters, potential recuperation ratio, and stroke outcomes. Patients with favorable collateral status exhibited smaller core infarct and penumbra volumes, higher mismatch ratios, better potential for recuperation, and improved functional outcomes compared to patients with unfavorable or intermediate collateral status.","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141273610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-30DOI: 10.3390/neurolint16030045
Helen Shen, Bella B Huasen, Murray C Killingsworth, Sonu M M Bhaskar
Objective: This study aims to develop and validate the Futile Recanalization Prediction Score (FRPS), a novel tool designed to predict the severity risk of FR and aid in pre- and post-EVT risk assessments. Methods: The FRPS was developed using a rigorous process involving the selection of predictor variables based on clinical relevance and potential impact. Initial equations were derived from previous meta-analyses and refined using various statistical techniques. We employed machine learning algorithms, specifically random forest regression, to capture nonlinear relationships and enhance model performance. Cross-validation with five folds was used to assess generalizability and model fit. Results: The final FRPS model included variables such as age, sex, atrial fibrillation (AF), hypertension (HTN), diabetes mellitus (DM), hyperlipidemia, cognitive impairment, pre-stroke modified Rankin Scale (mRS), systolic blood pressure (SBP), onset-to-puncture time, sICH, and NIHSS score. The random forest model achieved a mean R-squared value of approximately 0.992. Severity ranges for FRPS scores were defined as mild (FRPS < 66), moderate (FRPS 66-80), and severe (FRPS > 80). Conclusions: The FRPS provides valuable insights for treatment planning and patient management by predicting the severity risk of FR. This tool may improve the identification of candidates most likely to benefit from EVT and enhance prognostic accuracy post-EVT. Further clinical validation in diverse settings is warranted to assess its effectiveness and reliability.
{"title":"Introducing the Futile Recanalization Prediction Score (FRPS): A Novel Approach to Predict and Mitigate Ineffective Recanalization after Endovascular Treatment of Acute Ischemic Stroke.","authors":"Helen Shen, Bella B Huasen, Murray C Killingsworth, Sonu M M Bhaskar","doi":"10.3390/neurolint16030045","DOIUrl":"10.3390/neurolint16030045","url":null,"abstract":"<p><p><i>Objective</i>: This study aims to develop and validate the Futile Recanalization Prediction Score (FRPS), a novel tool designed to predict the severity risk of FR and aid in pre- and post-EVT risk assessments. <i>Methods</i>: The FRPS was developed using a rigorous process involving the selection of predictor variables based on clinical relevance and potential impact. Initial equations were derived from previous meta-analyses and refined using various statistical techniques. We employed machine learning algorithms, specifically random forest regression, to capture nonlinear relationships and enhance model performance. Cross-validation with five folds was used to assess generalizability and model fit. <i>Results:</i> The final FRPS model included variables such as age, sex, atrial fibrillation (AF), hypertension (HTN), diabetes mellitus (DM), hyperlipidemia, cognitive impairment, pre-stroke modified Rankin Scale (mRS), systolic blood pressure (SBP), onset-to-puncture time, sICH, and NIHSS score. The random forest model achieved a mean R-squared value of approximately 0.992. Severity ranges for FRPS scores were defined as mild (FRPS < 66), moderate (FRPS 66-80), and severe (FRPS > 80). <i>Conclusions</i>: The FRPS provides valuable insights for treatment planning and patient management by predicting the severity risk of FR. This tool may improve the identification of candidates most likely to benefit from EVT and enhance prognostic accuracy post-EVT. Further clinical validation in diverse settings is warranted to assess its effectiveness and reliability.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11206671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-20DOI: 10.3390/neurolint16030044
Thomas Kapapa, Stefanie Jesuthasan, Frederike Schiller, Franziska Schiller, Marcel Oehmichen, Dieter Woischneck, B. Mayer, Andrej Pala
Objective: There is a relationship between the incidence of spontaneous intracerebral haemorrhage (ICH) and age. The incidence increases with age. This study aims to facilitate the decision-making process in the treatment of ICH. It therefore investigated the outcome after ICH and decompressive craniectomy (DC) in older adults (>65 years of age). Methods: Retrospective, multicentre, descriptive observational study including only consecutive patients who received DC as the consequence of ICH. Additive evacuation of ICH was performed after the individual decision of the neurosurgeon. Besides demographic data, clinical outcomes both at discharge and 12 months after surgery were evaluated according to the Glasgow Outcome Scale (GOS). Patients were divided into age groups of ≤65 and >65 years and cohorts with favourable outcome (GOS IV–V) and unfavourable outcome (GOS I to III). Results: 56 patients were treated. Mean age was 53.3 (SD: 16.13) years. There were 41 (73.2%) patients aged ≤65 years and 15 (26.8%) patients aged >65 years. During hospital stay, 10 (24.4%) patients in the group of younger (≤65 years) and 5 (33.3%) in the group of older patients (>65 years) died. Mean time between ictus and surgery was 44.4 (SD: 70.79) hours for younger and 27.9 (SD: 41.71) hours for older patients. A disturbance of the pupillary function on admission occurred in 21 (51.2%) younger and 2 (13.3%) older patients (p = 0.014). Mean arterial pressure was 99.9 (SD: 17.00) mmHg for younger and 112.9 (21.80) mmHg in older patients. After 12 months, there was no significant difference in outcome between younger patients (≤65 years) and older patients (>65 years) after ICH and DC (p = 0.243). Nevertheless, in the group of younger patients (≤65 years), 9% had a very good and 15% had a good outcome. There was no good recovery in the group of older patients (>65 years). Conclusion: Patients >65 years of age treated with microsurgical haematoma evacuation and DC after ICH are likely to have a poor outcome. Furthermore, in the long term, only a few older adults have a good functional outcome with independence in daily life activities.
目的：自发性脑内出血（ICH）的发病率与年龄有关。年龄越大，发病率越高。本研究旨在促进治疗 ICH 的决策过程。因此，本研究调查了老年人（年龄大于 65 岁）ICH 和减压开颅术 (DC) 后的疗效。研究方法回顾性、多中心、描述性观察研究，仅包括因 ICH 而接受 DC 的连续患者。根据神经外科医生的个人决定，对 ICH 进行加量排空。除人口统计学数据外，还根据格拉斯哥结果量表（GOS）评估了出院时和术后12个月的临床结果。患者年龄分为小于 65 岁和大于 65 岁两组，以及预后良好（格拉斯哥预后量表 IV 至 V 级）和预后不良（格拉斯哥预后量表 I 至 III 级）两组。结果56名患者接受了治疗。平均年龄为 53.3 岁（标准差：16.13）。年龄小于 65 岁的患者有 41 人（73.2%），年龄大于 65 岁的患者有 15 人（26.8%）。住院期间，年龄较小（≤65 岁）的患者中有 10 人（24.4%）死亡，年龄较大（>65 岁）的患者中有 5 人（33.3%）死亡。年轻患者从发病到手术的平均时间为 44.4 小时（标清：70.79 小时），老年患者为 27.9 小时（标清：41.71 小时）。21 名（51.2%）年轻患者和 2 名（13.3%）老年患者入院时出现瞳孔功能紊乱（P = 0.014）。年轻患者的平均动脉压为 99.9（标度：17.00）毫米汞柱，老年患者为 112.9（21.80）毫米汞柱。12 个月后，ICH 和 DC 后的年轻患者（≤65 岁）和老年患者（>65 岁）的预后无明显差异（P = 0.243）。不过，在年轻患者组（≤65 岁）中，9% 的患者恢复得很好，15% 的患者恢复得很好。年龄较大的患者组（大于 65 岁）则没有很好的恢复。结论ICH 后接受显微外科血肿清除和 DC 治疗的 65 岁以上患者的预后可能较差。此外，从长远来看，只有少数老年人的功能恢复较好，可以独立进行日常生活活动。
{"title":"Outcome after Intracerebral Haemorrhage and Decompressive Craniectomy in Older Adults","authors":"Thomas Kapapa, Stefanie Jesuthasan, Frederike Schiller, Franziska Schiller, Marcel Oehmichen, Dieter Woischneck, B. Mayer, Andrej Pala","doi":"10.3390/neurolint16030044","DOIUrl":"https://doi.org/10.3390/neurolint16030044","url":null,"abstract":"Objective: There is a relationship between the incidence of spontaneous intracerebral haemorrhage (ICH) and age. The incidence increases with age. This study aims to facilitate the decision-making process in the treatment of ICH. It therefore investigated the outcome after ICH and decompressive craniectomy (DC) in older adults (>65 years of age). Methods: Retrospective, multicentre, descriptive observational study including only consecutive patients who received DC as the consequence of ICH. Additive evacuation of ICH was performed after the individual decision of the neurosurgeon. Besides demographic data, clinical outcomes both at discharge and 12 months after surgery were evaluated according to the Glasgow Outcome Scale (GOS). Patients were divided into age groups of ≤65 and >65 years and cohorts with favourable outcome (GOS IV–V) and unfavourable outcome (GOS I to III). Results: 56 patients were treated. Mean age was 53.3 (SD: 16.13) years. There were 41 (73.2%) patients aged ≤65 years and 15 (26.8%) patients aged >65 years. During hospital stay, 10 (24.4%) patients in the group of younger (≤65 years) and 5 (33.3%) in the group of older patients (>65 years) died. Mean time between ictus and surgery was 44.4 (SD: 70.79) hours for younger and 27.9 (SD: 41.71) hours for older patients. A disturbance of the pupillary function on admission occurred in 21 (51.2%) younger and 2 (13.3%) older patients (p = 0.014). Mean arterial pressure was 99.9 (SD: 17.00) mmHg for younger and 112.9 (21.80) mmHg in older patients. After 12 months, there was no significant difference in outcome between younger patients (≤65 years) and older patients (>65 years) after ICH and DC (p = 0.243). Nevertheless, in the group of younger patients (≤65 years), 9% had a very good and 15% had a good outcome. There was no good recovery in the group of older patients (>65 years). Conclusion: Patients >65 years of age treated with microsurgical haematoma evacuation and DC after ICH are likely to have a poor outcome. Furthermore, in the long term, only a few older adults have a good functional outcome with independence in daily life activities.","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141122757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-14DOI: 10.3390/neurolint16030043
A. Baroni, Annibale Antonioni, G. Fregna, N. Lamberti, Fabio Manfredini, Giacomo Koch, A. D'Ausilio, S. Straudi
Paired associative stimulation (PAS) is a non-invasive brain stimulation technique combining transcranial magnetic stimulation and peripheral nerve stimulation. PAS allows connections between cortical areas and peripheral nerves (C/P PAS) or between cortical regions (C/C PAS) to be strengthened or weakened by spike-timing-dependent neural plasticity mechanisms. Since PAS modulates both neurophysiological features and motor performance, there is growing interest in its application in neurorehabilitation. We aimed to synthesize evidence on the motor rehabilitation role of PAS in stroke patients. We performed a literature search following the PRISMA Extension for Scoping Reviews Framework. Eight studies were included: one investigated C/C PAS between the cerebellum and the affected primary motor area (M1), seven applied C/P PAS over the lesional, contralesional, or both M1. Seven studies evaluated the outcome on upper limb and one on lower limb motor recovery. Although several studies omit crucial methodological details, PAS highlighted effects mainly on corticospinal excitability, and, more rarely, an improvement in motor performance. However, most studies failed to prove a correlation between neurophysiological changes and motor improvement. Although current studies seem to suggest a role of PAS in post-stroke rehabilitation, their heterogeneity and limited number do not yet allow definitive conclusions to be drawn.
配对联想刺激（PAS）是一种结合经颅磁刺激和周围神经刺激的非侵入式脑刺激技术。配对联想刺激允许通过尖峰计时神经可塑性机制加强或削弱大脑皮层区域与周围神经之间（C/P PAS）或大脑皮层区域之间（C/C PAS）的连接。由于 PAS 可调节神经生理特征和运动表现，人们对其在神经康复中的应用越来越感兴趣。我们旨在综合有关 PAS 在中风患者运动康复中作用的证据。我们按照 PRISMA 扩展范围综述框架进行了文献检索。共纳入八项研究：一项研究调查了小脑和受影响的初级运动区（M1）之间的 C/C PAS，七项研究在病变、对侧或两个 M1 上应用了 C/P PAS。七项研究评估了上肢运动恢复情况，一项研究评估了下肢运动恢复情况。尽管有几项研究遗漏了关键的方法细节，但 PAS 主要突出了对皮质脊髓兴奋性的影响，更罕见的是对运动表现的改善。然而，大多数研究都未能证明神经生理学变化与运动能力改善之间的相关性。尽管目前的研究似乎表明了脑卒中后康复训练的作用，但这些研究的异质性和数量有限，还无法得出明确的结论。
{"title":"The Effectiveness of Paired Associative Stimulation on Motor Recovery after Stroke: A Scoping Review","authors":"A. Baroni, Annibale Antonioni, G. Fregna, N. Lamberti, Fabio Manfredini, Giacomo Koch, A. D'Ausilio, S. Straudi","doi":"10.3390/neurolint16030043","DOIUrl":"https://doi.org/10.3390/neurolint16030043","url":null,"abstract":"Paired associative stimulation (PAS) is a non-invasive brain stimulation technique combining transcranial magnetic stimulation and peripheral nerve stimulation. PAS allows connections between cortical areas and peripheral nerves (C/P PAS) or between cortical regions (C/C PAS) to be strengthened or weakened by spike-timing-dependent neural plasticity mechanisms. Since PAS modulates both neurophysiological features and motor performance, there is growing interest in its application in neurorehabilitation. We aimed to synthesize evidence on the motor rehabilitation role of PAS in stroke patients. We performed a literature search following the PRISMA Extension for Scoping Reviews Framework. Eight studies were included: one investigated C/C PAS between the cerebellum and the affected primary motor area (M1), seven applied C/P PAS over the lesional, contralesional, or both M1. Seven studies evaluated the outcome on upper limb and one on lower limb motor recovery. Although several studies omit crucial methodological details, PAS highlighted effects mainly on corticospinal excitability, and, more rarely, an improvement in motor performance. However, most studies failed to prove a correlation between neurophysiological changes and motor improvement. Although current studies seem to suggest a role of PAS in post-stroke rehabilitation, their heterogeneity and limited number do not yet allow definitive conclusions to be drawn.","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140981646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-13DOI: 10.3390/neurolint16030042
Ali A. Mohamed, Willy Gan, Denis Babici, Veronica Hagan, Raphael Wald, Marc Swerdloff
(1) Background: Niemann–Pick type C1 (NP-C1) is a lysosomal storage disorder that results in the defective trafficking of cholesterol and other cellular lipids in the endosomal–lysosomal pathway. This rare autosomal recessive disorder presents in three forms based on the age of onset. The adult form presents in patients greater than 15 years of age but is rarely seen after the age of 30. Common symptoms of the late adult-onset category of NP-C1 include progressive cognitive impairment and ataxia, with psychiatric and movement disorders presenting less frequently than in other forms of NP-C1. Dystonic movement disorders present most frequently, along with chorea, myoclonus, and parkinsonism. Herein, we present a rare case of NP-C1, diagnosed at age 35 with an initial symptom of supranuclear palsy. The goal of the presented case is to highlight the importance of the neurological examination and an inclusive differential diagnosis in patients with new-onset supranuclear palsy. (2) Methods: A single case report. (3) Results: A 46-year-old male with a past medical history of NP-C1 was admitted to the hospital for respiratory distress. He was noted to have a supranuclear gaze palsy with partially preserved voluntary saccades to the right. His mother revealed that he first had difficulty moving his eyes at the age of 34. After multiple consultations and genetic testing one year later, he was diagnosed with NP-C1. (4) Conclusions: Because NP-C1 affects many regions of the brain responsible for eye movements, neurological eye assessments can be a useful tool in diagnoses. Furthermore, eye movement abnormalities may be the initial presenting symptom of NP-C1, predisposing patients to misdiagnosis with progressive supranuclear palsy and other conditions that may mimic early-stage NP-C1. Definitive diagnosis is achieved through genetic testing. Filipin staining test was the gold standard in the past. The NP-C Suspicion Index was developed to assist in diagnoses, but its efficacy is unclear with late adult-onset NP-C1. Although no cure exists, early identification can facilitate an improved symptom management course for patients. Miglustat, a glucosylceramide synthase (GCS) inhibitor, is the approved therapy in Europe specific to NP-C1 for slowing and preventing the neurological manifestations of NP-C1. Delays between symptom onset and treatment initiation are likely to result in poorer outcomes and a progression of neurological symptoms. High doses may present tolerance concerns, especially in cases of delayed treatment and advanced neurological deficit.
{"title":"Supranuclear Palsy as an Initial Presentation of the Adult-Onset Niemann-Pick Type C","authors":"Ali A. Mohamed, Willy Gan, Denis Babici, Veronica Hagan, Raphael Wald, Marc Swerdloff","doi":"10.3390/neurolint16030042","DOIUrl":"https://doi.org/10.3390/neurolint16030042","url":null,"abstract":"(1) Background: Niemann–Pick type C1 (NP-C1) is a lysosomal storage disorder that results in the defective trafficking of cholesterol and other cellular lipids in the endosomal–lysosomal pathway. This rare autosomal recessive disorder presents in three forms based on the age of onset. The adult form presents in patients greater than 15 years of age but is rarely seen after the age of 30. Common symptoms of the late adult-onset category of NP-C1 include progressive cognitive impairment and ataxia, with psychiatric and movement disorders presenting less frequently than in other forms of NP-C1. Dystonic movement disorders present most frequently, along with chorea, myoclonus, and parkinsonism. Herein, we present a rare case of NP-C1, diagnosed at age 35 with an initial symptom of supranuclear palsy. The goal of the presented case is to highlight the importance of the neurological examination and an inclusive differential diagnosis in patients with new-onset supranuclear palsy. (2) Methods: A single case report. (3) Results: A 46-year-old male with a past medical history of NP-C1 was admitted to the hospital for respiratory distress. He was noted to have a supranuclear gaze palsy with partially preserved voluntary saccades to the right. His mother revealed that he first had difficulty moving his eyes at the age of 34. After multiple consultations and genetic testing one year later, he was diagnosed with NP-C1. (4) Conclusions: Because NP-C1 affects many regions of the brain responsible for eye movements, neurological eye assessments can be a useful tool in diagnoses. Furthermore, eye movement abnormalities may be the initial presenting symptom of NP-C1, predisposing patients to misdiagnosis with progressive supranuclear palsy and other conditions that may mimic early-stage NP-C1. Definitive diagnosis is achieved through genetic testing. Filipin staining test was the gold standard in the past. The NP-C Suspicion Index was developed to assist in diagnoses, but its efficacy is unclear with late adult-onset NP-C1. Although no cure exists, early identification can facilitate an improved symptom management course for patients. Miglustat, a glucosylceramide synthase (GCS) inhibitor, is the approved therapy in Europe specific to NP-C1 for slowing and preventing the neurological manifestations of NP-C1. Delays between symptom onset and treatment initiation are likely to result in poorer outcomes and a progression of neurological symptoms. High doses may present tolerance concerns, especially in cases of delayed treatment and advanced neurological deficit.","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140985354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-10DOI: 10.3390/neurolint16030041
Małgorzata Wiszniewska, Urszula Włodarczyk, Magdalena Sury, Artur Słomka, Natalia Piekuś-Słomka, Anna Żdanowicz, Ewa Żekanowska
Background and Aims: In recent years, there has been a growing interest in factor XIII in ischaemic stroke. The study’s main aim was to assess the usefulness of factor XIII concentration determination in patients with acute ischaemic stroke (AIS) treated with thrombolysis with recombinant tissue plasminogen activator (t-PA). Methods: The study was conducted in two groups of 84 patients with AIS: group I—with thrombolytic therapy and group II—without thrombolysis. A physical examination, neurological status (using the National Institutes of Health Stroke Scale, NIHSS), daily patients’ activities measured with the Barthel Index and Modified Rankin Scale (mRS), and blood parameters were conducted on day 1 and day 7. The following parameters were assessed: highly sensitive C-reaction protein (CRP), fibrinogen, D-dimers (DD), neutrophil–lymphocyte ratio (NLR index), and the concentration of factor XIII-A. Results: In group I, the concentration of XIII-A decreased significantly between day 1 and 7 (p < 0.001). In group I, the concentration of XIII-A on day 7 in Total Anterior Circulation Infarct (TACI) was significantly lower than in non-TACI stroke. XIII-A concentration in group I was significantly lower in patients < 31 points with Acute Stroke Registry and Analysis of Lausanne (ASTRAL). A greater decrease in XIII-A between the first sampling on day 1 and the second sampling on day 7 was associated with a worse patient neurological state in group I. Conclusions: In patients with AIS treated with t-PA, factor XIII concentrations decrease in the acute phase of stroke, and the largest decrease occurs in the TACI stroke. Determination of factor XIII concentration in patients with AIS can be used in clinical practice as an additional parameter supporting the assessment of stroke severity and may play a role in the prognosis; lower factor XIII-A activity may be a predictor of a worse prognosis.
{"title":"The Usefulness of Factor XIII Concentration Assessment in Patients in the Acute Phase of Ischaemic Stroke Treated with Thrombolysis","authors":"Małgorzata Wiszniewska, Urszula Włodarczyk, Magdalena Sury, Artur Słomka, Natalia Piekuś-Słomka, Anna Żdanowicz, Ewa Żekanowska","doi":"10.3390/neurolint16030041","DOIUrl":"https://doi.org/10.3390/neurolint16030041","url":null,"abstract":"Background and Aims: In recent years, there has been a growing interest in factor XIII in ischaemic stroke. The study’s main aim was to assess the usefulness of factor XIII concentration determination in patients with acute ischaemic stroke (AIS) treated with thrombolysis with recombinant tissue plasminogen activator (t-PA). Methods: The study was conducted in two groups of 84 patients with AIS: group I—with thrombolytic therapy and group II—without thrombolysis. A physical examination, neurological status (using the National Institutes of Health Stroke Scale, NIHSS), daily patients’ activities measured with the Barthel Index and Modified Rankin Scale (mRS), and blood parameters were conducted on day 1 and day 7. The following parameters were assessed: highly sensitive C-reaction protein (CRP), fibrinogen, D-dimers (DD), neutrophil–lymphocyte ratio (NLR index), and the concentration of factor XIII-A. Results: In group I, the concentration of XIII-A decreased significantly between day 1 and 7 (p < 0.001). In group I, the concentration of XIII-A on day 7 in Total Anterior Circulation Infarct (TACI) was significantly lower than in non-TACI stroke. XIII-A concentration in group I was significantly lower in patients < 31 points with Acute Stroke Registry and Analysis of Lausanne (ASTRAL). A greater decrease in XIII-A between the first sampling on day 1 and the second sampling on day 7 was associated with a worse patient neurological state in group I. Conclusions: In patients with AIS treated with t-PA, factor XIII concentrations decrease in the acute phase of stroke, and the largest decrease occurs in the TACI stroke. Determination of factor XIII concentration in patients with AIS can be used in clinical practice as an additional parameter supporting the assessment of stroke severity and may play a role in the prognosis; lower factor XIII-A activity may be a predictor of a worse prognosis.","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140993973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-09DOI: 10.3390/neurolint16030040
T. Lysikova, A. Tomašcová, M. Kovalska, J. Lehotský, Katarina Leskova Majdova, Peter Kaplán, Z. Tatarkova
It is well known that the brain is quite vulnerable to oxidative stress, initiating neuronal loss after ischemia-reperfusion (IR) injury. A potent protective mechanism is ischemic preconditioning (IPC), where proteins are among the primary targets. This study explores redox-active proteins’ role in preserving energy supply. Adult rats were divided into the control, IR, and IPC groups. Protein profiling was conducted to identify modified proteins and then verified through activity assays, immunoblot, and immunohistochemical analyses. IPC protected cortex mitochondria, as evidenced by a 2.26-fold increase in superoxide dismutase (SOD) activity. Additionally, stable core subunits of respiratory chain complexes ensured sufficient energy production, supported by a 16.6% increase in ATP synthase activity. In hippocampal cells, IPC led to the downregulation of energy-related dehydrogenases, while a significantly higher level of peroxiredoxin 6 (PRX6) was observed. Notably, IPC significantly enhanced glutathione reductase activity to provide sufficient glutathione to maintain PRX6 function. Astrocytes may mobilize PRX6 to protect neurons during initial ischemic events, by decreased PRX6 positivity in astrocytes, accompanied by an increase in neurons following both IR injury and IPC. Maintained redox signaling via astrocyte-neuron communication triggers IPC’s protective state. The partnership among PRX6, SOD, and glutathione reductase appears essential in safeguarding and stabilizing the hippocampus.
{"title":"Dynamics in Redox-Active Molecules Following Ischemic Preconditioning in the Brain","authors":"T. Lysikova, A. Tomašcová, M. Kovalska, J. Lehotský, Katarina Leskova Majdova, Peter Kaplán, Z. Tatarkova","doi":"10.3390/neurolint16030040","DOIUrl":"https://doi.org/10.3390/neurolint16030040","url":null,"abstract":"It is well known that the brain is quite vulnerable to oxidative stress, initiating neuronal loss after ischemia-reperfusion (IR) injury. A potent protective mechanism is ischemic preconditioning (IPC), where proteins are among the primary targets. This study explores redox-active proteins’ role in preserving energy supply. Adult rats were divided into the control, IR, and IPC groups. Protein profiling was conducted to identify modified proteins and then verified through activity assays, immunoblot, and immunohistochemical analyses. IPC protected cortex mitochondria, as evidenced by a 2.26-fold increase in superoxide dismutase (SOD) activity. Additionally, stable core subunits of respiratory chain complexes ensured sufficient energy production, supported by a 16.6% increase in ATP synthase activity. In hippocampal cells, IPC led to the downregulation of energy-related dehydrogenases, while a significantly higher level of peroxiredoxin 6 (PRX6) was observed. Notably, IPC significantly enhanced glutathione reductase activity to provide sufficient glutathione to maintain PRX6 function. Astrocytes may mobilize PRX6 to protect neurons during initial ischemic events, by decreased PRX6 positivity in astrocytes, accompanied by an increase in neurons following both IR injury and IPC. Maintained redox signaling via astrocyte-neuron communication triggers IPC’s protective state. The partnership among PRX6, SOD, and glutathione reductase appears essential in safeguarding and stabilizing the hippocampus.","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140995121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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