Pub Date : 2025-03-01DOI: 10.1016/j.nrleng.2022.09.008
J. Tejada García , L.B. Lara Lezama , R. de la Fuente Blanco , A. Pérez de Prado , L. Benavente Fernández , M. Rico Santos , M.D. Fernández Couto , L. Naya Ríos , I. Couso Pazó , P.V. Alba , L. Redondo-Robles , L. López Mesonero , S. Arias-Rivas , M. Santamaría Cadavid , H. Tejada Meza , L. Horna Cañete , I. Azkune Calle , A. Pinedo Brochado , J.M. García Sánchez , I. Caballero Romero , M. Martínez Zabaleta
Introduction
There is an extending use of percutaneous closure of patent foramen ovale (PFO) as therapy for PFO-associated cryptogenic strokes. The aim of our study was to investigate the clinical practice of percutaneous closure of PFO and to analyse the variables for decision-making on the selection of patients for this procedure.
Method
A prospective observational multicentric survey was conducted using all the cases of cryptogenic stroke/transient ischaemic attack associated with PFO recorded in the NORDICTUS hospital registry during the period 2018-2021. Clinical data, radiological patterns, echocardiogram data and factors related to PFO-associated stroke (thromboembolic disease and paradoxical embolism criteria) were recorded. The indication for closure was analysed according to age (≤/> 60 years) and the characteristics of the PFO.
Results
In the group ≤ 60 years (n = 488), 143 patients (29.3%) underwent PFO closure. The most influential variables for this therapy were detection of a high-risk PFO (OR 4.11; IC 2.6-6.5, P < .001), criteria for paradoxical embolism (OR 2.61; IC 1.28−5.28; P = .008) and previous use of antithrombotics (OR 2.67; IC 1.38−5.18; P = .009). In the > 60 years group (n = 124), 24 patients had PFO closure (19%). The variables related to this option were history of pulmonary thromboembolism, predisposition to thromboembolic disease, paradoxical embolism criteria, and high-risk PFO.
Conclusions
The detection of a high-risk PFO (large shunt, shunt with associated aneurysm) is the main criterion for a percutaneous closure-based therapy. Other conditions to consider in the eligibility of patients are the history of thromboembolic disease, paradoxical embolism criteria or the previous use of antithrombotics.
{"title":"Selection of patients for percutaneous closure in nonlacunar cryptogenic stroke associated with patent foramen ovale. Data from the NORDICTUS cooperative registry","authors":"J. Tejada García , L.B. Lara Lezama , R. de la Fuente Blanco , A. Pérez de Prado , L. Benavente Fernández , M. Rico Santos , M.D. Fernández Couto , L. Naya Ríos , I. Couso Pazó , P.V. Alba , L. Redondo-Robles , L. López Mesonero , S. Arias-Rivas , M. Santamaría Cadavid , H. Tejada Meza , L. Horna Cañete , I. Azkune Calle , A. Pinedo Brochado , J.M. García Sánchez , I. Caballero Romero , M. Martínez Zabaleta","doi":"10.1016/j.nrleng.2022.09.008","DOIUrl":"10.1016/j.nrleng.2022.09.008","url":null,"abstract":"<div><h3>Introduction</h3><div>There is an extending use of percutaneous closure of patent foramen ovale (PFO) as therapy for PFO-associated cryptogenic strokes. The aim of our study was to investigate the clinical practice of percutaneous closure of PFO and to analyse the variables for decision-making on the selection of patients for this procedure.</div></div><div><h3>Method</h3><div>A prospective observational multicentric survey was conducted using all the cases of cryptogenic stroke/transient ischaemic attack associated with PFO recorded in the NORDICTUS hospital registry during the period 2018-2021. Clinical data, radiological patterns, echocardiogram data and factors related to PFO-associated stroke (thromboembolic disease and paradoxical embolism criteria) were recorded. The indication for closure was analysed according to age (≤/> 60 years) and the characteristics of the PFO.</div></div><div><h3>Results</h3><div>In the group ≤ 60 years (n = 488), 143 patients (29.3%) underwent PFO closure. The most influential variables for this therapy were detection of a high-risk PFO (OR 4.11; IC 2.6-6.5, <em>P</em> < .001), criteria for paradoxical embolism (OR 2.61; IC 1.28−5.28; <em>P</em> = .008) and previous use of antithrombotics (OR 2.67; IC 1.38−5.18; <em>P</em> = .009). In the > 60 years group (n = 124), 24 patients had PFO closure (19%). The variables related to this option were history of pulmonary thromboembolism, predisposition to thromboembolic disease, paradoxical embolism criteria, and high-risk PFO.</div></div><div><h3>Conclusions</h3><div>The detection of a high-risk PFO (large shunt, shunt with associated aneurysm) is the main criterion for a percutaneous closure-based therapy. Other conditions to consider in the eligibility of patients are the history of thromboembolic disease, paradoxical embolism criteria or the previous use of antithrombotics.</div></div>","PeriodicalId":94155,"journal":{"name":"Neurologia","volume":"40 2","pages":"Pages 139-149"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40474072","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 : 2025-03-01DOI: 10.1016/j.nrleng.2023.04.008
D. Santos García , J. Pagonabarraga Mora , F. Escamilla Sevilla , P.J. García Ruiz , J. Infante Ceberio , J. Kulisevsky Bojarski , G. Linazasoro Cristóbal , M.R. Luquín Piudo , J.C. Martínez Castrillo , S. Jesús Maestre , L. Vela Desojo , F.J. Campos Lucas , F. Caballero Martínez , P. Mir , Panel of Experts Phase 1
Background
Different types of therapies were proven effective for the medical management of motor and non-motor symptoms in Parkinson’s disease (PD). We aimed to gain consensus on the dopamine agonist (DA) therapy use in different clinical scenarios of Parkinson’s disease (PD) patients.
Methods
This consensus study was based on the nominal group technique. Initially, a consensus group comprising 12 expert neurologists in the PD field identified the topics to be addressed and elaborated different evidence-based preliminary statements. Next, a panel of 48 Spanish neurologists expressed their opinion on an internet-based systematic voting program. Finally, initial ideas were reviewed and rewritten according to panel contribution and were ranked by the consensus group using a Likert-type scale. The analysis of data was carried out by using a combination of both qualitative and quantitative methods. The consensus was achieved if the statement reached ≥ 3.5 points in the voting process.
Results
The consensus group produced 76 real-world recommendations. The topics addressed included 12 statements related to DA therapy in early PD, 20 statements concerning DA treatment strategy in patients with motor complications, 11 statements associated with DA drugs and their side effects, and 33 statements regarding DA therapy in specific clinical scenarios. The consensus group did not reach a consensus on 15 statements.
Conclusion
The findings from this consensus method represent an exploratory step to help clinicians and patients in the appropriate use of DA in different stages and clinical situations of PD.
{"title":"Dopamine agonist therapy in Parkinson’s disease: Spanish expert consensus on its use in different clinical situations","authors":"D. Santos García , J. Pagonabarraga Mora , F. Escamilla Sevilla , P.J. García Ruiz , J. Infante Ceberio , J. Kulisevsky Bojarski , G. Linazasoro Cristóbal , M.R. Luquín Piudo , J.C. Martínez Castrillo , S. Jesús Maestre , L. Vela Desojo , F.J. Campos Lucas , F. Caballero Martínez , P. Mir , Panel of Experts Phase 1","doi":"10.1016/j.nrleng.2023.04.008","DOIUrl":"10.1016/j.nrleng.2023.04.008","url":null,"abstract":"<div><h3>Background</h3><div>Different types of therapies were proven effective for the medical management of motor and non-motor symptoms in Parkinson’s disease (PD). We aimed to gain consensus on the dopamine agonist (DA) therapy use in different clinical scenarios of Parkinson’s disease (PD) patients.</div></div><div><h3>Methods</h3><div>This consensus study was based on the nominal group technique. Initially, a consensus group comprising 12 expert neurologists in the PD field identified the topics to be addressed and elaborated different evidence-based preliminary statements. Next, a panel of 48 Spanish neurologists expressed their opinion on an internet-based systematic voting program. Finally, initial ideas were reviewed and rewritten according to panel contribution and were ranked by the consensus group using a Likert-type scale. The analysis of data was carried out by using a combination of both qualitative and quantitative methods. The consensus was achieved if the statement reached ≥ 3.5 points in the voting process.</div></div><div><h3>Results</h3><div>The consensus group produced 76 real-world recommendations. The topics addressed included 12 statements related to DA therapy in early PD, 20 statements concerning DA treatment strategy in patients with motor complications, 11 statements associated with DA drugs and their side effects, and 33 statements regarding DA therapy in specific clinical scenarios. The consensus group did not reach a consensus on 15 statements.</div></div><div><h3>Conclusion</h3><div>The findings from this consensus method represent an exploratory step to help clinicians and patients in the appropriate use of DA in different stages and clinical situations of PD.</div></div>","PeriodicalId":94155,"journal":{"name":"Neurologia","volume":"40 2","pages":"Pages 171-181"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9779042","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 : 2025-03-01DOI: 10.1016/j.nrleng.2022.12.001
U. Gómez-Pinedo , L. Torre-Fuentes , J.A. Matías-Guiu , V. Pytel , D.D. Ojeda-Hernández , B. Selma-Calvo , P. Montero-Escribano , L. Vidorreta-Ballesteros , J. Matías-Guiu
Introduction
Several studies have analysed the presence of P2RX7 variants in patients with MS, reporting diverging results.
Methods
Our study analyses P2RX7 variants detected through whole-exome sequencing (WES).
Results
We analysed P2RX7, P2RX4, and CAMKK2 gene variants detected by whole-exome sequencing in all living members (n = 127) of 21 families including at least 2 individuals with multiple sclerosis. P2RX7 gene polymorphisms previously associated with autoimmune disease. Although no differences were observed between individuals with and without multiple sclerosis, we found greater polymorphism of gain-of-function variants of P2RX7 in families with individuals with multiple sclerosis than in the general population. Copresence of gain-of-function and loss-of-function variants was not observed to reduce the risk of presenting the disease. Three families displayed heterozygous gain-of-function SNPs in patients with multiple sclerosis but not in healthy individuals. We were unable to determine the impact of copresence of P2RX4 and CAMKK2 variants with P2RX7 variants, or the potential effect of the different haplotypes described in the gene. No clinical correlations with other autoimmune diseases were observed in our cohort.
Conclusions
Our results support the hypothesis that the disease is polygenic and point to a previously unknown mechanism of genetic predisposition to familial forms of multiple sclerosis. P2RX7 gene activity can be modified, which suggests the possibility of preventive pharmacological treatments for families including patients with familial multiple sclerosis.
{"title":"Exonic variants of the P2RX7 gene in familial multiple sclerosis","authors":"U. Gómez-Pinedo , L. Torre-Fuentes , J.A. Matías-Guiu , V. Pytel , D.D. Ojeda-Hernández , B. Selma-Calvo , P. Montero-Escribano , L. Vidorreta-Ballesteros , J. Matías-Guiu","doi":"10.1016/j.nrleng.2022.12.001","DOIUrl":"10.1016/j.nrleng.2022.12.001","url":null,"abstract":"<div><h3>Introduction</h3><div>Several studies have analysed the presence of <em>P2RX7</em> variants in patients with MS, reporting diverging results.</div></div><div><h3>Methods</h3><div>Our study analyses <em>P2RX7</em> variants detected through whole-exome sequencing (WES).</div></div><div><h3>Results</h3><div>We analysed <em>P2RX7</em>, <em>P2RX4</em>, and <em>CAMKK2</em> gene variants detected by whole-exome sequencing in all living members (n = 127) of 21 families including at least 2 individuals with multiple sclerosis. <em>P2RX7</em> gene polymorphisms previously associated with autoimmune disease. Although no differences were observed between individuals with and without multiple sclerosis, we found greater polymorphism of gain-of-function variants of <em>P2RX7</em> in families with individuals with multiple sclerosis than in the general population. Copresence of gain-of-function and loss-of-function variants was not observed to reduce the risk of presenting the disease. Three families displayed heterozygous gain-of-function SNPs in patients with multiple sclerosis but not in healthy individuals. We were unable to determine the impact of copresence of <em>P2RX4</em> and <em>CAMKK2</em> variants with <em>P2RX7</em> variants, or the potential effect of the different haplotypes described in the gene. No clinical correlations with other autoimmune diseases were observed in our cohort.</div></div><div><h3>Conclusions</h3><div>Our results support the hypothesis that the disease is polygenic and point to a previously unknown mechanism of genetic predisposition to familial forms of multiple sclerosis. <em>P2RX7</em> gene activity can be modified, which suggests the possibility of preventive pharmacological treatments for families including patients with familial multiple sclerosis.</div></div>","PeriodicalId":94155,"journal":{"name":"Neurologia","volume":"40 2","pages":"Pages 150-160"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10375400","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 : 2025-03-01DOI: 10.1016/j.nrleng.2024.02.001
J. Martín Prieto , E. García-Serrano Fuertes , J. Iglesias Bermejillo , A. Luna Rodríguez
{"title":"Mutations in the type IV collagen gen (COL4A1) as an unusual etiology of cerebrovascular disease in young adults","authors":"J. Martín Prieto , E. García-Serrano Fuertes , J. Iglesias Bermejillo , A. Luna Rodríguez","doi":"10.1016/j.nrleng.2024.02.001","DOIUrl":"10.1016/j.nrleng.2024.02.001","url":null,"abstract":"","PeriodicalId":94155,"journal":{"name":"Neurologia","volume":"40 2","pages":"Pages 217-220"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934937","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 : 2025-03-01DOI: 10.1016/j.nrleng.2025.02.001
A. Barragán-Prieto , S. Pérez-Sánchez , M. Castellanos , A. González , J. Montaner
Introduction
In recent years, telestroke programmes have been established as a fundamental tool for extending acute stroke care to hospitals that lack an on-call neurology service. The main objective of this study is to describe the existence and functioning of the different telestroke systems and networks (TS) in Spain.
Methods
We conducted a cross-sectional study to analyse the current situation of TS in Spain using a structured survey distributed among the members of the Stroke Study Group of the Spanish Society of Neurology.
Results
Responses were received from 12 of the 17 Spanish autonomous communities, of which 10 had implemented TS. In addition, a literature search revealed that 2 other systems were in operation. Twelve of the 17 regions in the country have TS, achieving coverage of at least 20% of the Spanish population. Of these 10 TS, organisation was regional in 7, provincial in 2, and hospital-based in one. Most TS (9) included at least simple CT and angio-CT studies; 4 also included perfusion imaging. Nine TS operated with professional videoconferencing equipment. However, the suboptimal quality of examination via videoconferencing scan was the main problem identified in 50% of TS. Other problems detected are difficulty obtaining data from registries and the transfer of images between hospitals.
Conclusion
In recent years, a significant expansion of telestroke programmes has taken place in Spain, which has improved the accessibility of specialised care in patients with symptoms of acute stroke. This study allows us to describe the different types of TS in Spain and to detect areas for improvement and expansion, and could contribute to defining regional telestroke implementation strategies to offer quality care to the whole population.
{"title":"The current situation of Telestroke in Spain","authors":"A. Barragán-Prieto , S. Pérez-Sánchez , M. Castellanos , A. González , J. Montaner","doi":"10.1016/j.nrleng.2025.02.001","DOIUrl":"10.1016/j.nrleng.2025.02.001","url":null,"abstract":"<div><h3>Introduction</h3><div>In recent years, telestroke programmes have been established as a fundamental tool for extending acute stroke care to hospitals that lack an on-call neurology service. The main objective of this study is to describe the existence and functioning of the different telestroke systems and networks (TS) in Spain.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional study to analyse the current situation of TS in Spain using a structured survey distributed among the members of the Stroke Study Group of the Spanish Society of Neurology.</div></div><div><h3>Results</h3><div>Responses were received from 12 of the 17 Spanish autonomous communities, of which 10 had implemented TS. In addition, a literature search revealed that 2 other systems were in operation. Twelve of the 17 regions in the country have TS, achieving coverage of at least 20% of the Spanish population. Of these 10 TS, organisation was regional in 7, provincial in 2, and hospital-based in one. Most TS (9) included at least simple CT and angio-CT studies; 4 also included perfusion imaging. Nine TS operated with professional videoconferencing equipment. However, the suboptimal quality of examination via videoconferencing scan was the main problem identified in 50% of TS. Other problems detected are difficulty obtaining data from registries and the transfer of images between hospitals.</div></div><div><h3>Conclusion</h3><div>In recent years, a significant expansion of telestroke programmes has taken place in Spain, which has improved the accessibility of specialised care in patients with symptoms of acute stroke. This study allows us to describe the different types of TS in Spain and to detect areas for improvement and expansion, and could contribute to defining regional telestroke implementation strategies to offer quality care to the whole population.</div></div>","PeriodicalId":94155,"journal":{"name":"Neurologia","volume":"40 2","pages":"Pages 182-190"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415869","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 : 2025-03-01DOI: 10.1016/j.nrleng.2023.06.003
C. García-Muñoz , J.C. Hernández-Rodríguez , J.J. Pereyra-Rodriguez
Background
Mortality in Parkinson’s disease is increasing worldwide, but Spanish data need further study.
Objective
To analyse the mortality trends of Parkinson’s disease in Spain between 1981 and 2020.
Methods
This observational retrospective study assessed the Parkinson’s disease mortality data from 1981 to 2020 collected from the National Statistics Institute of Spain. Age-standardised mortality rates were analysed by age and sex groups, detecting significant mortality trends through a joinpoint analysis. Age-period-cohort effect and potential years of life lost analyses were conducted. The European standard population of 2013 was considered for the analyses.
Results
A total of 88 034 deaths were assessed. The overall age-standardised mortality rate rose throughout the period from 3.67 to 8.57 per 100 000 inhabitants. Mortality rates in men were higher than in women, 11.63 versus 6.57 deaths per 100 000 inhabitants. The sex ratio showed an increase in premature mortality in men during 2020. The overall joinpoint analysis recorded a rise in mortality, primarily since the 20th century, mainly in male and older groups, that matched with a period effect. The age effect was detected, confirming higher mortality at an older age. The analysis of potential years of life lost detected a growth in this rate, changing from 0.66 in 1981 to 1.06 in 2020.
Conclusions
Mortality data for Parkinson’s disease in Spain rose significantly in forty years. Mortality rate was higher in the male and age group above 75 years of age. The sex ratio showed premature mortality in men in 2020, which will need further study.
{"title":"Mortality rates for Parkinson’s disease are increasing in Spain. An age-period-cohort and joinpoint analysis of mortality rates from 1981 to 2020","authors":"C. García-Muñoz , J.C. Hernández-Rodríguez , J.J. Pereyra-Rodriguez","doi":"10.1016/j.nrleng.2023.06.003","DOIUrl":"10.1016/j.nrleng.2023.06.003","url":null,"abstract":"<div><h3>Background</h3><div>Mortality in Parkinson’s disease is increasing worldwide, but Spanish data need further study.</div></div><div><h3>Objective</h3><div>To analyse the mortality trends of Parkinson’s disease in Spain between 1981 and 2020.</div></div><div><h3>Methods</h3><div>This observational retrospective study assessed the Parkinson’s disease mortality data from 1981 to 2020 collected from the National Statistics Institute of Spain. Age-standardised mortality rates were analysed by age and sex groups, detecting significant mortality trends through a joinpoint analysis. Age-period-cohort effect and potential years of life lost analyses were conducted. The European standard population of 2013 was considered for the analyses.</div></div><div><h3>Results</h3><div>A total of 88 034 deaths were assessed. The overall age-standardised mortality rate rose throughout the period from 3.67 to 8.57 per 100 000 inhabitants. Mortality rates in men were higher than in women, 11.63 versus 6.57 deaths per 100 000 inhabitants. The sex ratio showed an increase in premature mortality in men during 2020. The overall joinpoint analysis recorded a rise in mortality, primarily since the 20th century, mainly in male and older groups, that matched with a period effect. The age effect was detected, confirming higher mortality at an older age. The analysis of potential years of life lost detected a growth in this rate, changing from 0.66 in 1981 to 1.06 in 2020.</div></div><div><h3>Conclusions</h3><div>Mortality data for Parkinson’s disease in Spain rose significantly in forty years. Mortality rate was higher in the male and age group above 75 years of age. The sex ratio showed premature mortality in men in 2020, which will need further study.</div></div>","PeriodicalId":94155,"journal":{"name":"Neurologia","volume":"40 2","pages":"Pages 161-170"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9770224","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 : 2025-03-01DOI: 10.1016/j.nrleng.2025.02.003
A.R. Ramos-Molina , A.R. Tejeda-Martínez , J.M. Viveros-Paredes , V. Chaparro-Huerta , M.F. Urmeneta-Ortíz , L.J. Ramírez-Jirano , M.E. Flores-Soto
Introduction
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Although the precise pathogenesis of PD remains unclear, several studies demonstrate that oxidative stress, inflammation, low levels of antioxidants, and the presence of biomolecules that generate reactive oxygen species can disrupt the blood–brain barrier (BBB) as an essential feature of the disease.
Aims
This study aimed to test whether agonism to cannabinoid receptor type 2 (CB2) through the administration of β-caryophyllene (BCP) could correct BBB permeability in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonism induction model.
Methods
We conducted a molecular assessment of proteins (immunochemistry and western blot), BBB permeability, and related biomarkers of PD (lipid peroxidation) in the MPTP mouse model of the disease.
Results
Expression of zonula occludens (ZO-1) and occludin tight junction (TJ) proteins was dampened in the striatum and substantia nigra pars compacta of mice, while lipid peroxidation and BBB permeability increased in the striatum in the MPTP-treated group, and these effects were reversed under BCP administration. This phytocannabinoid was able to restore protein expression and immunoreactivity of tyrosine hydroxylase (TH), ionized calcium-binding adapter molecule 1 (Iba-1), and glial fibrillary acidic protein (GFAP), as well as nuclear factor-erythroid 2-related factor (NRF2) translocation to the nucleus, and NADPH quinone oxidase 1 (NQO1) expression in mice treated with MPTP.
Conclusion
These results highlight the role of CB2 as a therapeutic target for PD, suggesting that its activation may ameliorate PD-related BBB disruption and oxidative stress, reducing the selective death of dopaminergic neurons.
{"title":"Beta-caryophyllene inhibits the permeability of the blood–brain barrier in MPTP-induced parkinsonism","authors":"A.R. Ramos-Molina , A.R. Tejeda-Martínez , J.M. Viveros-Paredes , V. Chaparro-Huerta , M.F. Urmeneta-Ortíz , L.J. Ramírez-Jirano , M.E. Flores-Soto","doi":"10.1016/j.nrleng.2025.02.003","DOIUrl":"10.1016/j.nrleng.2025.02.003","url":null,"abstract":"<div><h3>Introduction</h3><div>Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Although the precise pathogenesis of PD remains unclear, several studies demonstrate that oxidative stress, inflammation, low levels of antioxidants, and the presence of biomolecules that generate reactive oxygen species can disrupt the blood–brain barrier (BBB) as an essential feature of the disease.</div></div><div><h3>Aims</h3><div>This study aimed to test whether agonism to cannabinoid receptor type 2 (CB2) through the administration of β-caryophyllene (BCP) could correct BBB permeability in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonism induction model.</div></div><div><h3>Methods</h3><div>We conducted a molecular assessment of proteins (immunochemistry and western blot), BBB permeability, and related biomarkers of PD (lipid peroxidation) in the MPTP mouse model of the disease.</div></div><div><h3>Results</h3><div>Expression of zonula occludens (ZO-1) and occludin tight junction (TJ) proteins was dampened in the striatum and substantia nigra pars compacta of mice, while lipid peroxidation and BBB permeability increased in the striatum in the MPTP-treated group, and these effects were reversed under BCP administration. This phytocannabinoid was able to restore protein expression and immunoreactivity of tyrosine hydroxylase (TH), ionized calcium-binding adapter molecule 1 (Iba-1), and glial fibrillary acidic protein (GFAP), as well as nuclear factor-erythroid 2-related factor (NRF2) translocation to the nucleus, and NADPH quinone oxidase 1 (NQO1) expression in mice treated with MPTP.</div></div><div><h3>Conclusion</h3><div>These results highlight the role of CB2 as a therapeutic target for PD, suggesting that its activation may ameliorate PD-related BBB disruption and oxidative stress, reducing the selective death of dopaminergic neurons.</div></div>","PeriodicalId":94155,"journal":{"name":"Neurologia","volume":"40 2","pages":"Pages 191-203"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551470","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 : 2025-01-01DOI: 10.1016/j.nrleng.2022.07.003
M.-C. Boll , M. Alcaraz-Zubeldia , C. Rios , D. González-Esquivel , S. Montes
Background
Few treatments are currently available for amyotrophic lateral sclerosis (ALS). A combination of lithium carbonate and valproic acid (VPA-Li) was shown to inhibit motor neuron death and delay disease progression.
Methods
Outpatients with a typical ALS presentation were enrolled in a randomized, placebo-controlled trial to assess the efficacy of orally administered VPA-Li. Changes in a functional scale score (ALSFRS-R) and survival rate were chosen as primary outcome variables. Secondary outcome variables included BMI, respiratory monitoring, quality of life, and a global impression of the treatment.
Results
Out of 42 patients enrolled, 20 individuals receiving VPA-Li and 18 on placebo treatment were included in the final analysis. Forty-five percent of patients receiving VPA-Li completed the trial, whereas only 22.22% of patients in the placebo group attended the final visit 18 months later (P = 0.09). Major changes in the ALSFRS-R score were observed, including a decrease of 1.195 points/month in the placebo group (95% CI: 0.7869–1.6031) and of 0.5085 under VPA-Li treatment (95% CI: 0.2288–0.7882) between months 6 and 14. Adverse events included bad mouth taste, constipation, and anorexia. Survival rate, body weight, and quality of life were positive outcomes by the end of the trial despite a high sample reduction, especially in the placebo group. The inclusion of 212 subjects in each group would confirm these differences.
Conclusions
Combined VPA-Li treatment associated with slower ALS progression and better secondary outcomes. This dual treatment overcame the futility threshold and merits further investigation in ALS.
{"title":"A phase 2, double-blind, placebo-controlled trial of a valproate/lithium combination in ALS patients","authors":"M.-C. Boll , M. Alcaraz-Zubeldia , C. Rios , D. González-Esquivel , S. Montes","doi":"10.1016/j.nrleng.2022.07.003","DOIUrl":"10.1016/j.nrleng.2022.07.003","url":null,"abstract":"<div><h3>Background</h3><div>Few treatments are currently available for amyotrophic lateral sclerosis (ALS). A combination of lithium carbonate and valproic acid (VPA-Li) was shown to inhibit motor neuron death and delay disease progression.</div></div><div><h3>Methods</h3><div>Outpatients with a typical ALS presentation were enrolled in a randomized, placebo-controlled trial to assess the efficacy of orally administered VPA-Li. Changes in a functional scale score (ALSFRS-R) and survival rate were chosen as primary outcome variables. Secondary outcome variables included BMI, respiratory monitoring, quality of life, and a global impression of the treatment.</div></div><div><h3>Results</h3><div>Out of 42 patients enrolled, 20 individuals receiving VPA-Li and 18 on placebo treatment were included in the final analysis. Forty-five percent of patients receiving VPA-Li completed the trial, whereas only 22.22% of patients in the placebo group attended the final visit 18 months later (<em>P</em> = 0.09). Major changes in the ALSFRS-R score were observed, including a decrease of 1.195 points/month in the placebo group (95% CI: 0.7869–1.6031) and of 0.5085 under VPA-Li treatment (95% CI: 0.2288–0.7882) between months 6 and 14. Adverse events included bad mouth taste, constipation, and anorexia. Survival rate, body weight, and quality of life were positive outcomes by the end of the trial despite a high sample reduction, especially in the placebo group. The inclusion of 212 subjects in each group would confirm these differences.</div></div><div><h3>Conclusions</h3><div>Combined VPA-Li treatment associated with slower ALS progression and better secondary outcomes. This dual treatment overcame the futility threshold and merits further investigation in ALS.</div></div>","PeriodicalId":94155,"journal":{"name":"Neurologia","volume":"40 1","pages":"Pages 32-40"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40337078","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 : 2025-01-01DOI: 10.1016/j.nrleng.2022.06.005
Y. Rodríguez-Agudelo , M. Chávez-Oliveros , A. Ochoa-Morales , L. Martínez-Ruano , A. Camacho-Molina , F. Paz-Rodríguez
Introduction
Huntington's disease (HD) is a neurodegenerative and hereditary disorder. Due to the predictive diagnosis, incipient clinical characteristics have been described in the prodromal phase. Several studies have reported an increase in psychiatric symptoms in carriers of the HD gene without motor symptoms.
Objective
To identify psychological distress in carriers of the mutation that causes HD, without motor symptoms, utilizing the Symptom Checklist 90 (SCL-90), and to correlate with the burden and proximity of the disease.
Method
A sample of 175 participants in a HD Predictive Diagnostic Program (PDP-HD) was divided into HEP carriers (39.4%) and NPEH non-carriers (61.6%) of the HD-causing mutation. By means of mathematical formulas, the disease burden and proximity to the manifest stage in the PEH group were obtained and it was correlated with the results of the SCL-90-R.
Results
Comparing the results obtained in the SCL-90-R of the PEH and NPEH, the difference is observed in the positive somatic male index, where the PEH obtains higher average scores. The correlations between disease burden and psychological distress occur in the domains; obsessions and compulsions, interpersonal sensitivity, hostility, global severity index and positive somatic distress index. A low correlation is observed between the burden of disease and the scores obtained in psychological discomfort.
Conclusions
In general, we found that the PEH group obtained a higher score in the dimensions evaluated with the SCL-90-R, showing a relationship with the burden and differences due to the proximity of the disease. Higher scores on the SCL-90-R dimensions in carriers of the HD gene may suggest an early finding of psychological symptoms in the disease.
简介亨廷顿氏病（Huntington's disease，HD）是一种神经退行性遗传疾病。由于该病的诊断具有预测性，因此在前驱期就已描述了该病的初期临床特征。一些研究报告称，无运动症状的 HD 基因携带者的精神症状有所增加：目的：利用症状量表 90（SCL-90）确定无运动症状的 HD 基因突变携带者的心理困扰，并将其与疾病的负担和临近程度联系起来：方法：将参加 HD 预测诊断计划（PDP-HD）的 175 名参与者分为 HEP（39.4%）和 NPEH（61.6%）两类，前者为 HD 致病突变携带者，后者为非携带者。通过数学公式，得出了 PEH 组的疾病负担和接近显现阶段的程度，并将其与 SCL-90-R 的结果相关联：结果：对比 PEH 和 NPEH 的 SCL-90-R 结果，可以发现在阳性体质男性指数方面存在差异，PEH 的平均得分更高。疾病负担和心理困扰之间的相关性出现在以下领域：强迫症和强迫症、人际关系敏感性、敌意、整体严重性指数和阳性躯体困扰指数。疾病负担与心理不适得分之间的相关性较低：总的来说，我们发现 PEH 组在 SCL-90-R 的评估维度上得分较高，这显示出与疾病负担之间的关系以及因疾病远近而产生的差异。HD基因携带者在SCL-90-R各维度上的得分较高，这可能表明该疾病的心理症状发现较早。
{"title":"Psychological discomfort in carriers and non-carriers of the Huntington disease mutation and its relationship with disease burden","authors":"Y. Rodríguez-Agudelo , M. Chávez-Oliveros , A. Ochoa-Morales , L. Martínez-Ruano , A. Camacho-Molina , F. Paz-Rodríguez","doi":"10.1016/j.nrleng.2022.06.005","DOIUrl":"10.1016/j.nrleng.2022.06.005","url":null,"abstract":"<div><h3>Introduction</h3><div>Huntington's disease (HD) is a neurodegenerative and hereditary disorder. Due to the predictive diagnosis, incipient clinical characteristics have been described in the prodromal phase. Several studies have reported an increase in psychiatric symptoms in carriers of the HD gene without motor symptoms.</div></div><div><h3>Objective</h3><div>To identify psychological distress in carriers of the mutation that causes HD, without motor symptoms, utilizing the Symptom Checklist 90 (SCL-90), and to correlate with the burden and proximity of the disease.</div></div><div><h3>Method</h3><div>A sample of 175 participants in a HD Predictive Diagnostic Program (PDP-HD) was divided into HEP carriers (39.4%) and NPEH non-carriers (61.6%) of the HD-causing mutation. By means of mathematical formulas, the disease burden and proximity to the manifest stage in the PEH group were obtained and it was correlated with the results of the SCL-90-R.</div></div><div><h3>Results</h3><div>Comparing the results obtained in the SCL-90-R of the PEH and NPEH, the difference is observed in the positive somatic male index, where the PEH obtains higher average scores. The correlations between disease burden and psychological distress occur in the domains; obsessions and compulsions, interpersonal sensitivity, hostility, global severity index and positive somatic distress index. A low correlation is observed between the burden of disease and the scores obtained in psychological discomfort.</div></div><div><h3>Conclusions</h3><div>In general, we found that the PEH group obtained a higher score in the dimensions evaluated with the SCL-90-R, showing a relationship with the burden and differences due to the proximity of the disease. Higher scores on the SCL-90-R dimensions in carriers of the HD gene may suggest an early finding of psychological symptoms in the disease.</div></div>","PeriodicalId":94155,"journal":{"name":"Neurologia","volume":"40 1","pages":"Pages 1-9"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40344844","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 : 2025-01-01DOI: 10.1016/j.nrleng.2024.02.009
J. García-Ull , N. González-García , M. Torres-Ferrús , D. García-Azorín , I.F.J. Molina-Martínez , I. Beltrán-Blasco , S. Santos-Lasaosa , G. Latorre , A.B. Gago-Veiga , J.M. Láinez , J. Porta-Etessam , C. Nieves-Castellanos , A. Mínguez-Olaondo , A. López-Bravo , S. Quintas , N. Morollón , S. Díaz-Insa , R. Belvís , P. Irimia
Primary intracranial pressure disorders include idiopathic intracranial hypertension and spontaneous intracranial hypotension. Remarkable advances have been made in the diagnosis and treatment of these 2entities in recent years. Therefore, the Spanish Society of Neurology's Headache Study Group (GECSEN) deemed it necessary to prepare this consensus statement, including diagnostic and therapeutic algorithms to facilitate and improve the management of these disorders in clinical practice.
This document was created by a committee of experts belonging to GECSEN, and is based on a systematic review of the literature, incorporating the experience of the participants, and establishes practical recommendations with levels of evidence and grades of recommendation.
{"title":"Diagnosis and treatment of disorders of intracranial pressure: consensus statement of the Spanish Society of Neurology’s Headache Study Group","authors":"J. García-Ull , N. González-García , M. Torres-Ferrús , D. García-Azorín , I.F.J. Molina-Martínez , I. Beltrán-Blasco , S. Santos-Lasaosa , G. Latorre , A.B. Gago-Veiga , J.M. Láinez , J. Porta-Etessam , C. Nieves-Castellanos , A. Mínguez-Olaondo , A. López-Bravo , S. Quintas , N. Morollón , S. Díaz-Insa , R. Belvís , P. Irimia","doi":"10.1016/j.nrleng.2024.02.009","DOIUrl":"10.1016/j.nrleng.2024.02.009","url":null,"abstract":"<div><div>Primary intracranial pressure disorders include idiopathic intracranial hypertension and spontaneous intracranial hypotension. Remarkable advances have been made in the diagnosis and treatment of these 2entities in recent years. Therefore, the Spanish Society of Neurology's Headache Study Group (GECSEN) deemed it necessary to prepare this consensus statement, including diagnostic and therapeutic algorithms to facilitate and improve the management of these disorders in clinical practice.</div><div>This document was created by a committee of experts belonging to GECSEN, and is based on a systematic review of the literature, incorporating the experience of the participants, and establishes practical recommendations with levels of evidence and grades of recommendation.</div></div>","PeriodicalId":94155,"journal":{"name":"Neurologia","volume":"40 1","pages":"Pages 118-137"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140023880","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}
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