Pub Date : 2022-04-30DOI: 10.32440/ar.2022.139.01.rev06
A. Fernández, L. Gandía, A.G. García
Amyotrophic lateral sclerosis (ALS), an adult onset, fatal neurodegenerative disease, has as a cardinal pathogenic feature the selective death of motor neurons (MNs) at the cortex, brainstem, and spinal cord. In this review we focus on four aspects: (i) the hypothesis of disease propagation through the cerebrospinal fluid (CSF); (ii) the distortion of the exocytotic release of neurotransmitters at the sympathoadrenal axis; (iii) the ultrastructural and functional alterations of mitochondria from adrenal medullary chromaffin cells (CCs); and (iv) the purinergic P2X7 receptor (P2X7R) as a potential target for neuroprotection. Concerning disease propagation from one to another area of the central nervous system (CNS), the pattern of clinical progression suggests that the disease spreads centrifugally. This indicates that a kind of toxin agent may be released and propagated through the CSF. In our laboratory we found that CSF from ALS patients exerted toxic effects on cultured cortical MNs. In CCs, we found deep distortions of the exocytotic kinetics and the exocytotic fusion pore in the process of catecholamine release, in the SOD1G93A mouse model of ALS. Furthermore, we found that these alterations could be related to the accumulation of mutated SOD1 into mitochondria; this resulted in mitochondrial depolarization, excess production of reactive oxygen species and deficiency in oxidative phosphorylation. Finally, we discuss recent data on the potential therapeutic effect of compound JNJ-47965567, a blocker of P2X7Rs known to be central-stage in neuroinflammation. Upon its chronic administration to SOD1G93A, we found that the compound delayed disease onset but only in females mice. In conclusion, why MN selectively die in ALS disease, remains a mystery; On the other hand, it seems that other cell types are also affected, particularly at the sympathoadrenal axis. As disease pathogenesis remains obscure, the search of therapeutic targets to slow disease progression in ALS, remains puzzling.
{"title":"Amyotrophic lateral sclerosis is not only a motor neuron disease: impact of the sympathoadrenal axis","authors":"A. Fernández, L. Gandía, A.G. García","doi":"10.32440/ar.2022.139.01.rev06","DOIUrl":"https://doi.org/10.32440/ar.2022.139.01.rev06","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS), an adult onset, fatal neurodegenerative disease, has as a cardinal pathogenic feature the selective death of motor neurons (MNs) at the cortex, brainstem, and spinal cord. In this review we focus on four aspects: (i) the hypothesis of disease propagation through the cerebrospinal fluid (CSF); (ii) the distortion of the exocytotic release of neurotransmitters at the sympathoadrenal axis; (iii) the ultrastructural and functional alterations of mitochondria from adrenal medullary chromaffin cells (CCs); and (iv) the purinergic P2X7 receptor (P2X7R) as a potential target for neuroprotection.\u0000Concerning disease propagation from one to another area of the central nervous system (CNS), the pattern of clinical progression suggests that the disease spreads centrifugally. This indicates that a kind of toxin agent may be released and propagated through the CSF. In our laboratory we found that CSF from ALS patients exerted toxic effects on cultured cortical MNs.\u0000In CCs, we found deep distortions of the exocytotic kinetics and the exocytotic fusion pore in the process of catecholamine release, in the SOD1G93A mouse model of ALS. Furthermore, we found that these alterations could be related to the accumulation of mutated SOD1 into mitochondria; this resulted in mitochondrial depolarization, excess production of reactive oxygen species and deficiency in oxidative phosphorylation.\u0000Finally, we discuss recent data on the potential therapeutic effect of compound JNJ-47965567, a blocker of P2X7Rs known to be central-stage in neuroinflammation. Upon its chronic administration to SOD1G93A, we found that the compound delayed disease onset but only in females mice.\u0000In conclusion, why MN selectively die in ALS disease, remains a mystery; On the other hand, it seems that other cell types are also affected, particularly at the sympathoadrenal axis. As disease pathogenesis remains obscure, the search of therapeutic targets to slow disease progression in ALS, remains puzzling.","PeriodicalId":75487,"journal":{"name":"Anales de la Real Academia Nacional de Medicina","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42833877","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 : 2022-01-01DOI: 10.32440/ar.2022.139.01.rev02
J. R. de Berrazueta Fernández
In 1859 Charles Darwin in his “The Origin of Species” formulated three facts that explain the principle of evolution: the presence of a common ancestor, the existence of advantageous genetic mutations for survival and the elimination of unfavorable ones or Natural Selection. The embryological development of the mammalian heart improves the need for external oxygen uptake, transport and release in the tissues, which exists in all multicellular living beings from the most primitive and enables the function of all organs and systems. In invertebrates, such as insects, arthropods and molluscs, the open circulatory system reaches a development similar to that of human Carnegie stages 10-13: endocardial tubes, straight tube, or early stages of the bulboventricular loop. In vertebrates, the closed system of fish develops hearts with three and four chambers equivalent to the torsion phase of the loop in mammals, or the fifth week of human embryonic development, with a model closer to that of mammals appearing in reptiles with differences such as the incomplete septation of the ventricles and the development of two aortic trunks in crocodilians. Birds and mammals have reached a similar degree of embryonic development of their hearts, with four septate chambers, the same as the Cono Truncus one, and which separate the systemic and pulmonary circulation. All the embryological development of the human heart is completed between days 20 and 60 of gestation, concluding in the fetal phase its growth together with the rest of the organism.
{"title":"Phylogenetic evolution of the heart","authors":"J. R. de Berrazueta Fernández","doi":"10.32440/ar.2022.139.01.rev02","DOIUrl":"https://doi.org/10.32440/ar.2022.139.01.rev02","url":null,"abstract":"In 1859 Charles Darwin in his “The Origin of Species” formulated three facts that explain the principle of evolution: the presence of a common ancestor, the existence of advantageous genetic mutations for survival and the elimination of unfavorable ones or Natural Selection. The embryological development of the mammalian heart improves the need for external oxygen uptake, transport and release in the tissues, which exists in all multicellular living beings from the most primitive and enables the function of all organs and systems. In invertebrates, such as insects, arthropods and molluscs, the open circulatory system reaches a development similar to that of human Carnegie stages 10-13: endocardial tubes, straight tube, or early stages of the bulboventricular loop. In vertebrates, the closed system of fish develops hearts with three and four chambers equivalent to the torsion phase of the loop in mammals, or the fifth week of human embryonic development, with a model closer to that of mammals appearing in reptiles with differences such as the incomplete septation of the ventricles and the development of two aortic trunks in crocodilians. Birds and mammals have reached a similar degree of embryonic development of their hearts, with four septate chambers, the same as the Cono Truncus one, and which separate the systemic and pulmonary circulation. All the embryological development of the human heart is completed between days 20 and 60 of gestation, concluding in the fetal phase its growth together with the rest of the organism.","PeriodicalId":75487,"journal":{"name":"Anales de la Real Academia Nacional de Medicina","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69672377","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 : 2022-01-01DOI: 10.32440/ar.2022.139.01.supl01.art01
J.M. García Sagredo
{"title":"Memoria de la secretaría general del año 2021","authors":"J.M. García Sagredo","doi":"10.32440/ar.2022.139.01.supl01.art01","DOIUrl":"https://doi.org/10.32440/ar.2022.139.01.supl01.art01","url":null,"abstract":"","PeriodicalId":75487,"journal":{"name":"Anales de la Real Academia Nacional de Medicina","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69672411","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 : 2022-01-01DOI: 10.32440/ar.2022.139.01.ed01
M. Alaminos
{"title":"Artificial tissues as medicine of the future","authors":"M. Alaminos","doi":"10.32440/ar.2022.139.01.ed01","DOIUrl":"https://doi.org/10.32440/ar.2022.139.01.ed01","url":null,"abstract":"","PeriodicalId":75487,"journal":{"name":"Anales de la Real Academia Nacional de Medicina","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69672356","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 : 2022-01-01DOI: 10.32440/ar.2022.139.01.supl01.art03
A. Fernández-Cruz Pérez
{"title":"Sesión necrológica en memoria del Excmo. Sr. D. Alfredo Robledo Aguilar","authors":"A. Fernández-Cruz Pérez","doi":"10.32440/ar.2022.139.01.supl01.art03","DOIUrl":"https://doi.org/10.32440/ar.2022.139.01.supl01.art03","url":null,"abstract":"","PeriodicalId":75487,"journal":{"name":"Anales de la Real Academia Nacional de Medicina","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69671961","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 : 2022-01-01DOI: 10.32440/ar.2021.138.03.ed01
D. Gracia-Guillén
{"title":"The moral problem of vaccines","authors":"D. Gracia-Guillén","doi":"10.32440/ar.2021.138.03.ed01","DOIUrl":"https://doi.org/10.32440/ar.2021.138.03.ed01","url":null,"abstract":"","PeriodicalId":75487,"journal":{"name":"Anales de la Real Academia Nacional de Medicina","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69671939","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 : 2022-01-01DOI: 10.32440/ar.2022.139.01.org01
E. Fernández-Espejo
Objectives. Myeloperoxidase (MPO) has been implicated in Parkinson´s disease (PD). The objective was to look at the relationship of MPO concentration in serum and cerebrospinal fluid (CSF) with clinical variables of PD. Methods. In this prospective, observational, and cross-sectional study, MPO concentration in serum and the CSF was analyzed in 36 patients with idiopathic PD and 30 controls, who were enrolled from 2012 to 2017. In the group of patients, correlation of MPO content with demographic, clinical and tomographic variables was examined. The extent and degree of nigrostriatal dopaminergic cell loss was evaluated by using SPECT and 123I-Ioflupane, radioligand that has binding affinity for dopamine-transporter (DAT). Results. Serum MPO concentration, not CSF MPO content, was significantly higher in the patients (p<.0001). Significant correlation values were found between serum MPO concentration and rating scales of motor severity (Hoehn-Yahr, MDS-UPDRS part-III), and percentage reduction of DAT binding on basal ganglia (p<.0001). Patients with moderate-advanced disease (Hoehn-Yahr stage 3) showed significantly higher serum MPO content relative to patients with early disease (Hoehn-Yahr stages 1-2, p<.0001). DAT binding was reduced on all striatal regions, and signal reduction was higher in the putamen relative to the caudate nucleus (p<.0001). Percentage reduction of DAT binding on the striatum and putamen significantly correlated with rating scales of motor severity. Conclusions. Myeloperoxidase content in serum is increased in PD patients and correlates with motor severity degree and loss of dopamine-transporter binding on basal ganglia. The results allow proposing that the measurement of MPO level in serum could be useful for PD diagnosis, and that the inhibition of serum MPO would be a promising therapeutic tool. The study also confirms that the putamen shows higher reduction of DAT binding than the caudate nucleus, and degree of nigrostriatal dopaminergic cell loss is well quantified with rating scales of motor severity.
{"title":"Enhanced serum myeloperoxidase level correlates with clinical features of Parkinson's disease","authors":"E. Fernández-Espejo","doi":"10.32440/ar.2022.139.01.org01","DOIUrl":"https://doi.org/10.32440/ar.2022.139.01.org01","url":null,"abstract":"Objectives. Myeloperoxidase (MPO) has been implicated in Parkinson´s disease (PD). The objective was to look at the relationship of MPO concentration in serum and cerebrospinal fluid (CSF) with clinical variables of PD. Methods. In this prospective, observational, and cross-sectional study, MPO concentration in serum and the CSF was analyzed in 36 patients with idiopathic PD and 30 controls, who were enrolled from 2012 to 2017. In the group of patients, correlation of MPO content with demographic, clinical and tomographic variables was examined. The extent and degree of nigrostriatal dopaminergic cell loss was evaluated by using SPECT and 123I-Ioflupane, radioligand that has binding affinity for dopamine-transporter (DAT). Results. Serum MPO concentration, not CSF MPO content, was significantly higher in the patients (p<.0001). Significant correlation values were found between serum MPO concentration and rating scales of motor severity (Hoehn-Yahr, MDS-UPDRS part-III), and percentage reduction of DAT binding on basal ganglia (p<.0001). Patients with moderate-advanced disease (Hoehn-Yahr stage 3) showed significantly higher serum MPO content relative to patients with early disease (Hoehn-Yahr stages 1-2, p<.0001). DAT binding was reduced on all striatal regions, and signal reduction was higher in the putamen relative to the caudate nucleus (p<.0001). Percentage reduction of DAT binding on the striatum and putamen significantly correlated with rating scales of motor severity. Conclusions. Myeloperoxidase content in serum is increased in PD patients and correlates with motor severity degree and loss of dopamine-transporter binding on basal ganglia. The results allow proposing that the measurement of MPO level in serum could be useful for PD diagnosis, and that the inhibition of serum MPO would be a promising therapeutic tool. The study also confirms that the putamen shows higher reduction of DAT binding than the caudate nucleus, and degree of nigrostriatal dopaminergic cell loss is well quantified with rating scales of motor severity.","PeriodicalId":75487,"journal":{"name":"Anales de la Real Academia Nacional de Medicina","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69672370","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 : 2022-01-01DOI: 10.32440/ar.2022.139.01.supl01.art02
J. Ribera Casado
{"title":"Sesión Necrológica en Memoria del Excmo. Sr. D. Manuel Serrano Ríos","authors":"J. Ribera Casado","doi":"10.32440/ar.2022.139.01.supl01.art02","DOIUrl":"https://doi.org/10.32440/ar.2022.139.01.supl01.art02","url":null,"abstract":"","PeriodicalId":75487,"journal":{"name":"Anales de la Real Academia Nacional de Medicina","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69671949","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 : 2021-12-21DOI: 10.32440/ar.2021.138.03.rev01
S. Sosa-Estani, J. Alvar, J. Sancho, P. Aparicio Azcárraga, M. Ciscar, S. Gold, M. V. Labrador Cañadas, B. Pécoul, M. Rivero, L. Gerardo Castellanos
Chagas disease is grouped among the Neglected Tropical Diseases (NTD), according to the classification of WHO and among the Neglected Infectious Diseases susceptible to be eliminated according to PAHO (EID). Chagas disease is the most common NTD (or EID) in wide areas of South and Central America where the vector – an insect, which transmits the parasite Trypanosoma cruzi via its bite – and the great majority of patients live. However, due to population movements, this disease has now become a global problem, especially in the USA and Spain. The control of transmission by the vector or by blood transfusions has progressed considerably. However, transmission by other routes, namely oral and mother-to-child are still a challenge in regards of control and access to health care. In the countries where transmission by the vector doesn’t take place, vertical transmission is the main route of transmission. Taking into account that there is a huge gap in diagnosing and treating patients suffering from Chagas disease, early diagnosis and treatment of infected women in childbearing age, pregnant women and children, as well as asymptomatic infected people, is an important contribution towards the control of this disease which is potentially fatal if left untreated. Aiming for this objective, all available tools should be optimized and implemented. There are several countries and regions already implementing this strategy in this particular group of women and children. The advances achieved are a good example of the collaboration between organizations and institutions in the public and private sectors, although a greater political commitment is needed in order to achieve Chagas elimination as a public health problem by 2030 as promoted by the ETMI-Plus strategy established by PAHO, the new WHO-NTD road map, the UN sustainable development goals (SDG) and the program “No baby with Chagas” launched by the SEGIB.
{"title":"Interruption of mother-to-child transmission and detection and treatment of children of infected mothers as a contribution to eradicate Chagas disease in Europe","authors":"S. Sosa-Estani, J. Alvar, J. Sancho, P. Aparicio Azcárraga, M. Ciscar, S. Gold, M. V. Labrador Cañadas, B. Pécoul, M. Rivero, L. Gerardo Castellanos","doi":"10.32440/ar.2021.138.03.rev01","DOIUrl":"https://doi.org/10.32440/ar.2021.138.03.rev01","url":null,"abstract":"Chagas disease is grouped among the Neglected Tropical Diseases (NTD), according to the classification of WHO and among the Neglected Infectious Diseases susceptible to be eliminated according to PAHO (EID). Chagas disease is the most common NTD (or EID) in wide areas of South and Central America where the vector – an insect, which transmits the parasite Trypanosoma cruzi via its bite – and the great majority of patients live. However, due to population movements, this disease has now become a global problem, especially in the USA and Spain. The control of transmission by the vector or by blood transfusions has progressed considerably. However, transmission by other routes, namely oral and mother-to-child are still a challenge in regards of control and access to health care. In the countries where transmission by the vector doesn’t take place, vertical transmission is the main route of transmission. Taking into account that there is a huge gap in diagnosing and treating patients suffering from Chagas disease, early diagnosis and treatment of infected women in childbearing age, pregnant women and children, as well as asymptomatic infected people, is an important contribution towards the control of this disease which is potentially fatal if left untreated. Aiming for this objective, all available tools should be optimized and implemented. There are several countries and regions already implementing this strategy in this particular group of women and children. The advances achieved are a good example of the collaboration between organizations and institutions in the public and private sectors, although a greater political commitment is needed in order to achieve Chagas elimination as a public health problem by 2030 as promoted by the ETMI-Plus strategy established by PAHO, the new WHO-NTD road map, the UN sustainable development goals (SDG) and the program “No baby with Chagas” launched by the SEGIB.","PeriodicalId":75487,"journal":{"name":"Anales de la Real Academia Nacional de Medicina","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43096211","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 : 2021-08-31DOI: 10.32440/ar.2021.138.02.rev02
K. Rubia
This paper reviews the functional magnetic resonance imaging (fMRI) literature of Attention Deficit Hyperactivity Disorder (ADHD) of the past three decades and the modern neurotherapies that have used these biomarkers as targets for treatment. Meta-analyses of task-based fMRI studies have shown functional abnormalities in different domain-dependent frontal, striatal, parietal, and cerebellar regions in ADHD. Resting state fMRI studies confirm abnormalities in different fronto-striato-parietal cognitive control, dorsal and ventral attention networks. The frontal parts of these networks have been targeted by neurotherapeutics. Only three small-numbered studies so far have applied functional near infrared spectroscopy (NIRS) and fMRI-Neurofeedback to ADHD. Studies have mostly shown feasibility and some promising effects on clinical, cognitive or imaging measures which invite further testing in larger samples. Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) or inferior frontal cortex (IFC) has not shown promising effects so far on improving cognition or symptoms. Eighteen studies tested the effects of single or multi-session transcranial direct current stimulation (tDCS) of mostly left DLPFC on mostly cognitive functions with fewer studies targeting right DLPFC or IFC. Our meta-analysis of tDCS studies shows relatively small effects of improvement of cognitive function while insufficient studies have tested clinical efficacy. A proof of concept study of trigeminal nerve stimulation (TNS) showed promising medium size effects for improving clinical symptoms but requires replication in larger samples. In conclusion, neurotherapies are attractive due to minimal side effects and potential longer-term effects on brain plasticity which drugs cannot offer; however, they are still in their infancy. They require systematic testing of optimal protocols in large samples, including optimal site of stimulation/neurofeedback, optimal frequency of treatment sessions, or optimal stimulation amplitude. Importantly, they will need to show potential for individualised treatment by providing understanding of treatment response prediction.
{"title":"Neuroimaging and neurotherapeutics for Attention Deficit Hyperactivity Disorder (ADHD)","authors":"K. Rubia","doi":"10.32440/ar.2021.138.02.rev02","DOIUrl":"https://doi.org/10.32440/ar.2021.138.02.rev02","url":null,"abstract":"This paper reviews the functional magnetic resonance imaging (fMRI) literature of Attention Deficit Hyperactivity Disorder (ADHD) of the past three decades and the modern neurotherapies that have used these biomarkers as targets for treatment. Meta-analyses of task-based fMRI studies have shown functional abnormalities in different domain-dependent frontal, striatal, parietal, and cerebellar regions in ADHD. Resting state fMRI studies confirm abnormalities in different fronto-striato-parietal cognitive control, dorsal and ventral attention networks. The frontal parts of these networks have been targeted by neurotherapeutics. Only three small-numbered studies so far have applied functional near infrared spectroscopy (NIRS) and fMRI-Neurofeedback to ADHD. Studies have mostly shown feasibility and some promising effects on clinical, cognitive or imaging measures which invite further testing in larger samples. Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) or inferior frontal cortex (IFC) has not shown promising effects so far on improving cognition or symptoms. Eighteen studies tested the effects of single or multi-session transcranial direct current stimulation (tDCS) of mostly left DLPFC on mostly cognitive functions with fewer studies targeting right DLPFC or IFC. Our meta-analysis of tDCS studies shows relatively small effects of improvement of cognitive function while insufficient studies have tested clinical efficacy. A proof of concept study of trigeminal nerve stimulation (TNS) showed promising medium size effects for improving clinical symptoms but requires replication in larger samples. In conclusion, neurotherapies are attractive due to minimal side effects and potential longer-term effects on brain plasticity which drugs cannot offer; however, they are still in their infancy. They require systematic testing of optimal protocols in large samples, including optimal site of stimulation/neurofeedback, optimal frequency of treatment sessions, or optimal stimulation amplitude. Importantly, they will need to show potential for individualised treatment by providing understanding of treatment response prediction.","PeriodicalId":75487,"journal":{"name":"Anales de la Real Academia Nacional de Medicina","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42201684","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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