TY - JOUR AU - Wißfeld, J. AU - Abou, Assale T. AU - Cuevas-Rios, G. AU - Liao, H. AU - Neumann, H. TI - Therapeutic potential to target sialylation and SIGLECs in neurodegenerative and psychiatric diseases JF - FRONTIERS IN NEUROLOGY J2 - FRONT NEUR VL - 15 PY - 2024 SN - 1664-2295 DO - 10.3389/fneur.2024.1330874 UR - https://m2.mtmt.hu/api/publication/34815131 ID - 34815131 N1 - Institute of Reconstructive Neurobiology, Medical Faculty and University Hospital Bonn, University of Bonn, Bonn, Germany Florey Institute of Neuroscience and Mental Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia Export Date: 23 April 2024 Correspondence Address: Neumann, H.; Institute of Reconstructive Neurobiology, Germany; email: harald.neumann@uni-bonn.de Chemicals/CAS: neuropilin 2, 227018-38-4; nitric oxide, 10102-43-9 AB - Sialic acids, commonly found as the terminal carbohydrate on the glycocalyx of mammalian cells, are pivotal checkpoint inhibitors of the innate immune system, particularly within the central nervous system (CNS). Sialic acid-binding immunoglobulin-like lectins (SIGLECs) expressed on microglia are key players in maintaining microglial homeostasis by recognizing intact sialylation. The finely balanced sialic acid-SIGLEC system ensures the prevention of excessive and detrimental immune responses in the CNS. However, loss of sialylation and SIGLEC receptor dysfunctions contribute to several chronic CNS diseases. Genetic variants of SIGLEC3/CD33, SIGLEC11, and SIGLEC14 have been associated with neurodegenerative diseases such as Alzheimer’s disease, while sialyltransferase ST8SIA2 and SIGLEC4/MAG have been linked to psychiatric diseases such as schizophrenia, bipolar disorders, and autism spectrum disorders. Consequently, immune-modulatory functions of polysialic acids and SIGLEC binding antibodies have been exploited experimentally in animal models of Alzheimer’s disease and inflammation-induced CNS tissue damage, including retinal damage. While the potential of these therapeutic approaches is evident, only a few therapies to target either sialylation or SIGLEC receptors have been tested in patient clinical trials. Here, we provide an overview of the critical role played by the sialic acid-SIGLEC axis in shaping microglial activation and function within the context of neurodegeneration and synaptopathies and discuss the current landscape of therapies that target sialylation or SIGLECs. Copyright © 2024 Wißfeld, Abou Assale, Cuevas-Rios, Liao and Neumann. LA - English DB - MTMT ER - TY - JOUR AU - Hu, Yue AU - Zheng, Yadan AU - Yang, Yue AU - Fang, Wenfeng AU - Huang, Maomao AU - Li, Dan AU - Xu, Zhangyu AU - Xu, Fangyuan AU - Wang, Jianxiong TI - A bibliometric analysis of cerebral palsy from 2003 to 2022 JF - FRONTIERS IN NEUROLOGY J2 - FRONT NEUR VL - 15 PY - 2024 SP - 1 SN - 1664-2295 DO - 10.3389/fneur.2024.1292587 UR - https://m2.mtmt.hu/api/publication/34802424 ID - 34802424 LA - English DB - MTMT ER - TY - JOUR AU - Solbakken, G. AU - Løseth, S. AU - Frich, J.C. AU - Dietrichs, E. AU - Ørstavik, K. TI - Small and large fiber neuropathy in adults with myotonic dystrophy type 1 JF - FRONTIERS IN NEUROLOGY J2 - FRONT NEUR VL - 15 PY - 2024 SN - 1664-2295 DO - 10.3389/fneur.2024.1375218 UR - https://m2.mtmt.hu/api/publication/34801696 ID - 34801696 N1 - Institute of Clinical Medicine, University of Oslo, Oslo, Norway Department of Neurology, Rheumatology and Rehabilitation, Drammen Hospital, Vestre Viken Health Trust, Drammen, Norway Department of Clinical Medicine, The Arctic University of Norway, Tromsø, Norway Section of Clinical Neurophysiology, University Hospital of North Norway, Tromsø, Norway Institute of Health and Society, University of Oslo, Oslo, Norway Department of Neurology, Oslo University Hospital, Oslo, Norway Diakonhjemmet Hospital, Oslo, Norway Export Date: 19 April 2024 Correspondence Address: Solbakken, G.; Institute of Clinical Medicine, Norway; email: grosolba@gmail.com AB - Introduction: Myotonic dystrophy type 1 (DM1) is an inherited neuromuscular disorder that affects multiple organs. In this study, we investigated symptoms of pain and presence of small and large fiber neuropathy in the juvenile and adult form of DM1. Method: Twenty genetically verified DM1 patients were included. Pain was assessed, and neurological examination and investigations of the peripheral nervous system by quantification of small nerve fibers in skin biopsy, quantitative sensory testing and nerve conduction studies were performed. Results from skin biopsies were compared to healthy controls. Result: Seventeen patients reported chronic pain. Large and/or small fiber abnormalities were present in 50% of the patients. The intraepidermal nerve fiber density was significantly lower in the whole group of patients compared to healthy controls. Conclusion: Small-fiber neuropathy might be an important cause of pain in DM1. Copyright © 2024 Solbakken, Løseth, Frich, Dietrichs and Ørstavik. LA - English DB - MTMT ER - TY - JOUR AU - Tseng, S.-C. AU - Cherry, D. AU - Ko, M. AU - Fisher, S.R. AU - Furtado, M. AU - Chang, S.-H. TI - The effects of combined transcranial brain stimulation and a 4-week visuomotor stepping training on voluntary step initiation in persons with chronic stroke—a pilot study JF - FRONTIERS IN NEUROLOGY J2 - FRONT NEUR VL - 15 PY - 2024 SN - 1664-2295 DO - 10.3389/fneur.2024.1286856 UR - https://m2.mtmt.hu/api/publication/34801392 ID - 34801392 N1 - Neuromechanics Laboratory, Department of Physical Therapy, University of Texas Medical Branch, Galveston, TX, United States Department of Physical Therapy, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, United States Neuromuscular Plasticity Laboratory, Department of Physical Medicine and Rehabilitation, University of Texas Health Science Center at Houston, Houston, TX, United States Export Date: 19 April 2024 Correspondence Address: Tseng, S.-C.; Neuromechanics Laboratory, United States; email: shtseng@utmb.edu Tradenames: MatLAB, Mathworks; MATLAB, Mathworks, United States Manufacturers: Mathworks; Mathworks, United States Funding text 1: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported in part by awards to S-CT from Texas Physical Therapy Foundation and Texas Woman’s University Research Enhancement Program. AB - Purpose: Evidence suggests that transcranial direct current stimulation (tDCS) can enhance motor performance and learning of hand tasks in persons with chronic stroke (PCS). However, the effects of tDCS on the locomotor tasks in PCS are unclear. This pilot study aimed to: (1) determine aggregate effects of anodal tDCS combined with step training on improvements of the neural and biomechanical attributes of stepping initiation in a small cohort of persons with chronic stroke (PCS) over a 4-week training program; and (2) assess the feasibility and efficacy of this novel approach for improving voluntary stepping initiation in PCS. Methods: A total of 10 PCS were randomly assigned to one of two training groups, consisting of either 12 sessions of VST paired with a-tDCS (n = 6) or sham tDCS (s-tDCS, n = 4) over 4 weeks, with step initiation (SI) tests at pre-training, post-training, 1-week and 1-month follow-ups. Primary outcomes were: baseline vertical ground reaction force (B-vGRF), response time (RT) to initiate anticipatory postural adjustment (APA), and the retention of B-VGRF and RT. Results: a-tDCS paired with a 4-week VST program results in a significant increase in paretic weight loading at 1-week follow up. Furthermore, a-tDCS in combination with VST led to significantly greater retention of paretic BWB compared with the sham group at 1 week post-training. Clinical implications: The preliminary findings suggest a 4-week VST results in improved paretic limb weight bearing (WB) during SI in PCS. Furthermore, VST combined with a-tDCS may lead to better retention of gait improvements (NCT04437251) (https://classic.clinicaltrials.gov/ct2/show/NCT04437251). Copyright © 2024 Tseng, Cherry, Ko, Fisher, Furtado and Chang. LA - English DB - MTMT ER - TY - JOUR AU - Diana, L. AU - Casati, C. AU - Melzi, L. AU - Bianchi, Marzoli S. AU - Bolognini, N. TI - The effects of occipital and parietal tDCS on chronic visual field defects after brain injury JF - FRONTIERS IN NEUROLOGY J2 - FRONT NEUR VL - 15 PY - 2024 SN - 1664-2295 DO - 10.3389/fneur.2024.1340365 UR - https://m2.mtmt.hu/api/publication/34801334 ID - 34801334 N1 - Laboratory of Neuropsychology, Department of Neurorehabilitation Sciences, IRCCS Istituto Auxologico Italiano, Milan, Italy Neuro-Ophthalmology Center and Ocular Electrophysiology Laboratory, IRCCS Istituto Auxologico Italiano, Milan, Italy Department of Psychology, University of Milano-Bicocca and NeuroMI, Milan, Italy Export Date: 19 April 2024 Correspondence Address: Diana, L.; Laboratory of Neuropsychology, Italy; email: l.diana@auxologico.it Manufacturers: BrainStim, Italy Funding text 1: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Italian Ministry of Health - Ricerca Corrente. AB - Introduction: Homonymous visual field defects (HVFDs) following acquired brain lesions affect independent living by hampering several activities of everyday life. Available treatments are intensive and week- or month-long. Transcranial Direct current stimulation (tDCS), a plasticity-modulating non-invasive brain stimulation technique, could be combined with behavioral trainings to boost their efficacy or reduce treatment duration. Some promising attempts have been made pairing occipital tDCS with visual restitution training, however less is knows about which area/network should be best stimulated in association with compensatory approaches, aimed at improving exploratory abilities, such as multisensory trainings. Methods: In a proof-of-principle, sham-controlled, single-blind study, 15 participants with chronic HVFDs underwent four one-shot sessions of active or sham anodal tDCS applied over the ipsilesional occipital cortex, the ipsilesional or contralesional posterior parietal cortex. tDCS was delivered during a compensatory multisensory (audiovisual) training. Before and immediately after each tDCS session, participants carried out a visual detection task, and two visual search tasks (EF and Triangles search tests). Accuracy (ACC) and response times (RTs) were analyzed with generalized mixed models. We investigated differences in baseline performance, clinical-demographic and lesion factors between tDCS responders and non-responders, based on post-tDCS behavioral improvements. Lastly, we conducted exploratory analyses to compare left and right brain-damaged participants. Results: RTs improved after active ipsilesional occipital and parietal tDCS in the visual search tasks, while no changes in ACC were detected. Responders to ipsilesional occipital tDCS (Triangle task) had shorter disease duration and smaller lesions of the parietal cortex and the superior longitudinal fasciculus. On the other end, on the EF test, those participants with larger damage of the temporo-parietal cortex or the fronto-occipital white matter tracts showed a larger benefit from contralesional parietal tDCS. Overall, the visual search RTs improvements were larger in participants with right-sided hemispheric lesions. Conclusion: The present result shows the facilitatory effects of occipital and parietal tDCS combined with compensatory multisensory training on visual field exploration in HVFDs, suggesting a potential for the development of new neuromodulation treatments to improve visual scanning behavior in brain-injured patients. Copyright © 2024 Diana, Casati, Melzi, Bianchi Marzoli and Bolognini. LA - English DB - MTMT ER - TY - JOUR AU - Wu, X. AU - Wang, S. AU - Xue, T. AU - Tan, X. AU - Li, J. AU - Chen, Z. AU - Wang, Z. TI - Disease-modifying therapy in progressive multiple sclerosis: a systematic review and network meta-analysis of randomized controlled trials JF - FRONTIERS IN NEUROLOGY J2 - FRONT NEUR VL - 15 PY - 2024 SN - 1664-2295 DO - 10.3389/fneur.2024.1295770 UR - https://m2.mtmt.hu/api/publication/34784503 ID - 34784503 N1 - Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Jiangsu, Suzhou, China Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Jiangsu, Suzhou, China Export Date: 11 April 2024 Correspondence Address: Chen, Z.; Department of Neurosurgery and Brain and Nerve Research Laboratory, Jiangsu, China; email: zqchen6@163.com Correspondence Address: Wang, Z.; Department of Neurosurgery and Brain and Nerve Research Laboratory, Jiangsu, China; email: wangzhong761@163.com Chemicals/CAS: beta1a interferon, 145258-61-3, 74899-71-1, 194739-10-1; beta1b interferon, 90598-63-3, 145155-23-3; dimethyl fumarate, 624-49-7; fingolimod, 162359-56-0, 162359-55-9, 1967800-35-6; glatiramer, 147245-92-9, 28704-27-0; laquinimod, 248281-84-7, 248282-07-7; mitoxantrone, 65271-80-9, 70476-82-3; natalizumab, 189261-10-7; ocrelizumab, 637334-45-3; rituximab, 174722-31-7; siponimod, 1230487-85-0, 1230487-00-9, 1234627-85-0 Funding details: National Natural Science Foundation of China, NSFC, 81971171 Funding details: National Natural Science Foundation of China, NSFC Funding details: Science and Technology Program of Suzhou, SLT201906 Funding details: Science and Technology Program of Suzhou Funding details: GSWS2019002 Funding text 1: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (No. 81971171), the Suzhou Science and Technology Project (No. SLT201906), and the Suzhou Health Talents Training Project (No. GSWS2019002). AB - Background: Currently, disease-modifying therapies (DMTs) for progressive multiple sclerosis (PMS) are widely used in clinical practice. At the same time, there are a variety of drug options for DMTs, but the effect of the drugs that can better relieve symptoms and improve the prognosis are still inconclusive. Objectives: This systematic review aimed to evaluate the efficacy and safety of DMTs for PMS and to identify the best among these drugs. Methods: MEDLINE, EMBASE, the Cochrane Library, and clinicaltrials.gov were systematically searched to identify relevant studies published before 30 January, 2023. We assessed the certainty of the evidence using the confidence in the network meta-analysis (CINeMA) framework. We estimated the summary risk ratio (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes with 95% credible intervals (CrIs). Results: We included 18 randomized controlled trials (RCTs) involving 9,234 patients in the study. DMT can effectively control the disease progression of MS. Among them, mitoxantrone, siponimod, and ocrelizumab are superior to other drug options in delaying disease progression (high certainty). Mitoxantrone was the best (with high certainty) for mitigating deterioration (progression of disability). Ocrelizumab performed best on the pre- and post-treatment Timed 25-Foot Walk test (T25FW; low certainty), as did all other agents (RR range: 1.12–1.05). In the 9-Hole Peg Test (9HPT), natalizumab performed the best (high certainty), as did all other agents (RR range: 1.59–1.09). In terms of imaging, IFN-beta-1b performed better on the new T2 hypointense lesion on contrast, before and after treatment (high certainty), while siponimod performed best on the change from baseline in the total volume of lesions on T2-weighted image contrast before and after treatment (high certainty), and sWASO had the highest area under the curve (SUCRA) value (100%). In terms of adverse events (AEs), rituximab (RR 1.01), and laquinimod (RR 1.02) were more effective than the placebo (high certainty). In terms of serious adverse events (SAEs), natalizumab (RR 1.09), and ocrelizumab (RR 1.07) were safer than placebo (high certainty). Conclusion: DMTs can effectively control disease progression and reduce disease deterioration during the treatment of PMS. Systematic review registration: https://inplasy.com/?s=202320071, identifier: 202320071. Copyright © 2024 Wu, Wang, Xue, Tan, Li, Chen and Wang. LA - English DB - MTMT ER - TY - JOUR AU - Cobo-Calvo, Á. AU - Gómez-Ballesteros, R. AU - Orviz, A. AU - Díaz, Sánchez M. AU - Boyero, S. AU - Aguado-Valcarcel, M. AU - Sepúlveda, M. AU - Rebollo, P. AU - López-Laiz, P. AU - Maurino, J. AU - Téllez, Lara N. TI - Therapeutic inertia in the management of neuromyelitis optica spectrum disorder JF - FRONTIERS IN NEUROLOGY J2 - FRONT NEUR VL - 15 PY - 2024 SN - 1664-2295 DO - 10.3389/fneur.2024.1341473 UR - https://m2.mtmt.hu/api/publication/34781460 ID - 34781460 N1 - Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d’Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain Medical Department, Roche Farma, Madrid, Spain Department of Neurology, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain Department of Neurology, Hospital Universitario Virgen del Rocío, Seville, Spain Department of Neurology, Hospital Universitario Cruces, Bilbao, Spain Department of Neurology, Hospital Álvaro Cunqueiro, Vigo, Spain Department of Neurology, Hospital Clínic de Barcelona, Barcelona, Spain IQVIA, Madrid, Spain Department of Neurology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain Export Date: 10 April 2024 Correspondence Address: Cobo-Calvo, Á.; Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Spain; email: acobo@cem-cat.org Chemicals/CAS: aquaporin 4, 175960-54-0 Funding details: SL43671 Funding text 1: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was funded by the Medical Department of Roche Farma Spain (SL43671). The funding source had no role in the design of this study, data analysis and interpretation, review and approval of the manuscript or the decision to submit for publication. AB - Introduction and objective: Limited information is available on how neurologists make therapeutic decisions in neuromyelitis optica spectrum disorder (NMOSD), especially when new treatments with different mechanisms of action, administration, and safety profile are being approved. Decision-making can be complex under this uncertainty and may lead to therapeutic inertia (TI), which refers to lack of treatment initiation or intensification when therapeutic goals are not met. The study aim was to assess neurologists’ TI in NMOSD. Methods: An online, cross-sectional study was conducted in collaboration with the Spanish Society of Neurology. Neurologists answered a survey composed of demographic characteristics, professional background, and behavioral traits. TI was defined as the lack of initiation or intensification with high-efficacy treatments when there is evidence of disease activity and was assessed through five NMOSD aquaporin-4 positive (AQP4+) simulated case scenarios. A multivariate logistic regression analysis was used to determine the association between neurologists’ characteristics and TI. Results: A total of 78 neurologists were included (median interquartile range [IQR] age: 36.0 [29.0–46.0] years, 55.1% male, median [IQR] experience managing demyelinating conditions was 5.2 [3.0–11.1] years). The majority of participants were general neurologists (59.0%) attending a median (IQR) of 5.0 NMOSD patients (3.0–12.0) annually. Thirty participants (38.5%) were classified as having TI. Working in a low complexity hospital and giving high importance to patient’s tolerability/safety when choosing a treatment were predictors of TI. Conclusion: TI is a common phenomenon among neurologists managing NMOSD AQP4+. Identifying TI and implementing specific intervention strategies may be critical to improving therapeutic decisions and patient care. Copyright © 2024 Cobo-Calvo, Gómez-Ballesteros, Orviz, Díaz Sánchez, Boyero, Aguado-Valcarcel, Sepúlveda, Rebollo, López-Laiz, Maurino and Téllez Lara. LA - English DB - MTMT ER - TY - JOUR AU - Thiraworawong, T. AU - Pathonsmith, C. TI - Cilostazol-based dual antiplatelet treatment in ischemic stroke or transient ischemic attack patients with asymptomatic carotid artery disease: a propensity score matching analysis JF - FRONTIERS IN NEUROLOGY J2 - FRONT NEUR VL - 15 PY - 2024 SN - 1664-2295 DO - 10.3389/fneur.2024.1362124 UR - https://m2.mtmt.hu/api/publication/34780684 ID - 34780684 N1 - Export Date: 10 April 2024 Correspondence Address: Thiraworawong, T.; Division of Vascular Neurology, Thailand; email: thiraworawong.t@nit.go.th AB - Background: The optimal treatment for asymptomatic atherosclerotic carotid artery disease remains controversial. Data on the efficacy of antiplatelet agents and stroke outcomes are limited. This study aimed to examine the efficacy and safety of cilostazol-based dual antiplatelet therapy in patients with ischemic stroke or transient ischemic attack and asymptomatic carotid artery disease. Methods: This retrospective cohort study was conducted in a tertiary-care setting and included baseline characteristics and clinical outcomes of participants. The study included patients who had experienced first-ever ischemic stroke or transient ischemic attack and asymptomatic atherosclerotic carotid artery stenosis, with a minimum follow-up period of 1 year. Asymptomatic carotid artery stenosis refers to stenosis in patients without neurological symptoms referable to the carotid arteries. Propensity scores were estimated using a logistic regression model based on participants’ baseline characteristics. The efficacy outcome was the composite outcome of recurrent ischemic events and vascular-related death in patients with ischemic stroke or transient ischemic attack and asymptomatic carotid artery stenosis. The safety outcome was the occurrence of hemorrhagic complications such as intracranial hemorrhages or extracranial hemorrhages. The effectiveness of dual therapy compared to monotherapy was evaluated at various time points following the initiation of antiplatelet treatment. Results: This study included 516 patients with a 1-year follow-up period. At 1 year, composite events occurred in 10 (6.3%) patients in the dual antiplatelet group compared with 12 (7.6%) in the single antiplatelet group (HR, 0.74; 95% CI, 0.61–0.90; p = 0.024). Extracranial hemorrhage occurred in 12 (7.6%) patients in the dual antiplatelet group compared with nine (5.7%) in the single antiplatelet group (HR, 1.35; 95% CI, 1.13–1.48; p = 0.017). No intracranial hemorrhages were observed in this cohort. Conclusion: Patients with asymptomatic carotid artery stenosis who received cilostazol-based dual antiplatelet therapy had a lower risk of composite events but a higher risk of minor extracranial hemorrhage than those who received a single antiplatelet agent. Copyright © 2024 Thiraworawong and Pathonsmith. LA - English DB - MTMT ER - TY - JOUR AU - Schaefer, J.H. AU - Lieschke, F. AU - Urban, H. AU - Bohmann, F.O. AU - Gatzke, F. AU - Miesbach, W. TI - Feasibility and comparability of different platelet function tests in acute stroke with or without prior antiplatelet therapy JF - FRONTIERS IN NEUROLOGY J2 - FRONT NEUR VL - 15 PY - 2024 SN - 1664-2295 DO - 10.3389/fneur.2024.1361751 UR - https://m2.mtmt.hu/api/publication/34779375 ID - 34779375 N1 - Department of Neurology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany Department of Internal Medicine II, Haemostaseology and Haemophilia Centre, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany Export Date: 9 April 2024 Correspondence Address: Schaefer, J.H.; Department of Neurology, Germany; email: ja.schaefer@med.uni-frankfurt.de AB - Background: The clinical course of ischemic and hemorrhagic strokes can be influenced by the coagulation status of individual patients. The prior use of antiplatelet therapy (APT) such as acetylsalicylic acid (ASA) or P2Y12-antagonists has been inconsistently described as possibly increasing the risk of hemorrhagic transformation or expansion. Since clinical studies describing prior use of antiplatelet medication are overwhelmingly lacking specific functional tests, we aimed to implement testing in routine stroke care. Methods: We used fluorescence-activated cell sorting (FACS) with antibodies against CD61 for thrombocyte identification and CD62p or platelet activation complex-1 (PAC-1) to determine platelet activation. Aggregometry and automated platelet functioning analyzer (PFA-200) were employed to test thrombocyte reactivity. FACS and aggregometry samples were stimulated in vitro with arachidonic acid (AA) and adenosine diphosphate (ADP) to measure increase in CD62p-/PAC-1-expression or aggregation, respectively. Results: Between February and July 2023, 20 blood samples (n = 11 ischemic strokes; n = 7 hemorrhagic strokes; n = 2 controls) were acquired and analyzed within 24 h of symptom onset. N = 11 patients had taken ASA, n = 8 patients no APT and n = 1 ASA+clopidogrel. ASA intake compared to no APT was associated with lower CD62p expression after stimulation with AA on FACS analysis (median 15.8% [interquartile range {IQR} 12.6–37.2%] vs. 40.1% [IQR 20.3–56.3%]; p = 0.020), lower platelet aggregation (9.0% [IQR 7.0–12.0%] vs. 88.5% [IQR 11.8–92.0%]; p = 0.015) and longer time to plug formation with PFA-200 (248.0 s [IQR 157.0–297] vs. 121.5 s [IQR 99.8–174.3]; p = 0.027). Significant correlations were noted between AA-induced CD62p expression and aggregometry analysis (n = 18; ρ = 0.714; p < 0.001) as well as a negative correlation between CD62p increase and PFA clot formation time (n = 18; ρ = −0.613; p = 0.007). Sensitivity for ASA intake was highest for PFA (81.8% for values ≥155.5 s). The combination of ASA + clopidogrel also affected ADP-induced CD62p and PAC-1 expression. Conclusion: In the clinical setting it is feasible to use differentiated platelet analytics to determine alterations caused by antiplatelet therapy. Among the tests under investigation, PFA-200 showed the highest sensitivity for the intake of ASA in stroke patients. FACS analysis on the other hand might be able to provide a more nuanced approach to altered platelet reactivity. Copyright © 2024 Schaefer, Lieschke, Urban, Bohmann, Gatzke and Miesbach. LA - English DB - MTMT ER - TY - JOUR AU - Almudhry, M. AU - Prasad, C. AU - Rupar, C.A. AU - Tay, K.Y. AU - Prasad, A.N. TI - Long-term follow-up of an attenuated presentation of NAXE-related disease, a potentially actionable neurometabolic disease: a case report JF - FRONTIERS IN NEUROLOGY J2 - FRONT NEUR VL - 15 PY - 2024 SN - 1664-2295 DO - 10.3389/fneur.2024.1204848 UR - https://m2.mtmt.hu/api/publication/34768699 ID - 34768699 N1 - London Health Sciences Centre and Western University, London, ON, Canada Department of Neuroscience, King Fahad Specialist Hospital, Dammam, Saudi Arabia Department of Pediatrics, Section of Genetics and Metabolism, Western University, London, ON, Canada Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada Department of Medical Imaging, Western University, London, ON, Canada Departments of Pediatrics and Pediatric Neurology, Western University, London, ON, Canada Export Date: 4 April 2024 Correspondence Address: Prasad, A.N.; London Health Sciences Centre and Western UniversityCanada; email: narayan.prasad@lhsc.on.ca Chemicals/CAS: carnitine, 461-06-3, 541-15-1, 56-99-5; citalopram, 59729-33-8, 59729-32-7, 85118-27-0; nicotinamide, 11032-50-1, 98-92-0; nicotinamide adenine dinucleotide, 53-84-9; nicotinic acid, 54-86-4, 59-67-6; pyruvate dehydrogenase, 9014-20-4; riboflavin, 83-88-5; thiamine, 59-43-8, 67-03-8; ubiquinone, 1339-63-5 Funding text 1: The authors would like to thank the patient and his family for allowing us to share the information. We would also like to acknowledge the efforts of Mohammed A. Almudhry in preparing Supplementary Figure S1 (the Cellular NAD(P)HX repair system). AB - Background: Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy (PEBEL-1) is an autosomal recessive disorder whereby a fluctuating clinical course is exacerbated by febrile illnesses. Pathogenic NAD(P)HX epimerase (NAXE) gene mutations underpin this disorder. This mutation damages the metabolite repair system involved in regenerating crucial redox carriers. Longer survival has rarely been reported in this potentially actionable entity. Objectives: This case study aims to report a milder phenotype of a patient with NAXE gene mutation and his longitudinal follow-up of more than 20 years. Case report: A 24-year-old man first became symptomatic in infancy with frequent initial neurological decompensations in the setting of infections with subsequent clinical improvement followed by stability with residual cerebellar dysfunction. Clinical features noted over the years include chronic ataxia, nystagmus, ptosis, mild spasticity of lower limbs, and neuropsychiatric symptoms. Cerebellar and spinal cord atrophy were noted in cranial and spinal MR imaging. Biallelic homozygous variants in the NAXE gene (c.733 A>C) were identified on whole exome sequencing. Symptom management included the initiation of a mitochondrial cocktail with carnitine, coenzyme Q, and thiamine. Subsequently, niacin (Vitamin B3), which is involved in the cellular biosynthesis of NAD+, was added, given its potentially beneficial therapeutic impact. Conclusion: A missense homozygous variant in the NAXE gene is described in this patient with a milder clinical phenotype of the disease. Supplementation with niacin in addition to a mitochondrial cocktail presents a potential supportive therapeutic option to reduce disease progression. Copyright © 2024 Almudhry, Prasad, Rupar, Tay and Prasad. LA - English DB - MTMT ER -