Antonio Gil-nagel - Academia.edu (original) (raw)

Papers by Antonio Gil-nagel

The redefinition of classical electroclinical syndromes and the emergence of neurogenetics has le... more The redefinition of classical electroclinical syndromes and the emergence of neurogenetics has led to a revolution in the field of developmental and epileptic encephalopathies (DEEs). In this context, advances in genetic techniques are leading to the final diagnosis of a large proportion of patients with DEE. However, up to 50% of patients with DEE remain undiagnosed. For patients with uncertain genetic etiology, there is a pressing need for the implementation of new targeted treatments and precision medicine. In some undiagnosed patients, genetic reanalysis with further in-depth or reverse phenotyping are valuable diagnostic tools to clarify new variants of uncertain significance. In other cases, the implementation of new bioinformatic algorithms is required for the update and reassessment of previously generated genetic data. Moreover, many other clinical tools have been developed for the management of patients of DEEs after a negative or inconclusive genetic testing. In this review, we highlight advances and limitations of new diagnostic strategies used in DEE patients without a known genetic etiology. Finally, we provide a wide perspective on aspects that will need further research, especially in non-Mendelian inheritance DEEs, such as those related to somatic mosaicism of the central nervous system or epigenetic and oligogenic mechanisms.

Neuropsychologia, Feb 1, 2021

Decades of research have increased the understanding of the contribution of the anterior temporal... more Decades of research have increased the understanding of the contribution of the anterior temporal lobes (ATLs) to semantic cognition. Nonetheless, whether semantic processing of different types of information show a selective relationship with left and right ATLs, or whether semantic processing in the ATLs is independent of the modality of the input is currently unknown. There exists evidence supporting each of these alternatives. A fundamental objection to these findings is that they were obtained from studies with patients with brain damage affecting extensive regions, sometimes bilaterally. In the current study, we assessed a group of 38 temporal lobe epilepsy (TLE) patients with either left or right small epileptogenic lesions with a battery of commonly used semantic tasks that tested verbal and non-verbal semantic processing. We found that left TLE patients exhibited worse performance than controls on the verbal semantic tasks, as expected, but also on the non-verbal semantic task. On the other hand, performance of the right TLE group did not differ from controls on the non-verbal task, but was worse on a semantic fluency task. When performance between patient groups was compared, we found that left TLE not only did worse than right TLE on the naming task, but also on the non-verbal associative memory task. When considered together, current data do not support a strong view of input modality differences between left and right ATLs. Additionally, they provide evidence indicating that the left and right ATLs do not make similar contributions to a singular functional system for semantic representation.

Developmental Medicine & Child Neurology, Jul 21, 2023

AimTo describe the experiences and unmet medical care needs of a group of parents of children wit... more AimTo describe the experiences and unmet medical care needs of a group of parents of children with developmental and epileptic encephalopathies (DEEs) caused by the SCN1A, KCNQ2, CDKL5, PCDH19, and GNAO1 variants.MethodA qualitative descriptive study was conducted. Participants were recruited using purposeful sampling. The inclusion criteria consisted of parents of children with DEEs caused by the SCN1A, KCNQ2, CDKL5, PCDH19, or GNAO1 variants, aged between 4 and 10 years old. In total, 21 parents were included. Data were acquired via researcher field notes and in‐depth interviews. A thematic analysis was performed.ResultsThree main themes were identified: (1) managing symptoms: epileptic seizures are experienced with great uncertainty and are accompanied by cognitive, behavioural, and motor symptoms; (2) accepting treatment: the ideal medication regimen is a challenge and the decision to withdraw or start a new therapy falls on the parents; and (3) therapeutic relationship and medical care: behaviours related to the health professional can hinder the therapeutic relationship with the parents. Parents are apprehensive about going to the emergency department.InterpretationProfessionals in emergency departments should acquire better knowledge of DEEs, welcome parents, and improve treatment for the children. The results of this study can serve as a starting point for a roadmap of relevant caregiver‐reported outcomes in DEEs, to be implemented with new clinical trials and aetiology‐targeted therapies.

Neurología, Mar 1, 2016

The use of the Multiphasic Personality Inventory Minnesota 2 (MMPI-2) for the diagnosis of psycho... more The use of the Multiphasic Personality Inventory Minnesota 2 (MMPI-2) for the diagnosis of psychogenic non-epileptic seizures (PNES) is controversial. This study examines the validity of the clinical scales and, unlike previous works, the content scales. Cross-sectional study of 209 patients treated in the epilepsy unit. We performed a logistic regression analysis, taking video-electroencephalography as the reference test, and predictor variables age, sex, IQ and clinical (model A) or content scales (model B) of the MMPI-2. The models were selected according to the Aikake index and compared using the DeLong test. We analyzed 37 patients with PNES alone, or combined with seizures, and 172 patients with seizures only. The model consisting of sex, Hs (hypochondriasis) and Pa (paranoia) showed a sensitivity of 77.1%, a specificity of 76.8%, a percentage of correct classification of 76.8%, and an area under the curve (AUC) of 0.836 for diagnosing CNEP. Model B, consisting of sex, HEA (health concerns) and FRS (fears), showed a sensitivity of 65.7%, a specificity of 78.0%, a percentage of correct classification of 75.9% and an UUC of 0.840. DeLong's test did not detect significant differences. The MMPI-2 has a moderate validity for the diagnosis of PNES in patients referred to an epilepsy unit. Using content scales does not significantly improve results from the clinical scales.

Seizure-european Journal of Epilepsy, Aug 1, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Seminars in Neurology, Jul 1, 2008

Adverse effects of antiepileptic drugs (AEDs) are considered by patients to be at least as import... more Adverse effects of antiepileptic drugs (AEDs) are considered by patients to be at least as important as repetitive seizures in terms of quality of life. AED toxicity is frequent and contributes to a high proportion of treatment failures. Despite its high prevalence and clinical relevance, screening for adverse reactions to AEDs is not systematically included in everyday clinical practice; therefore it is very likely that it remains underestimated. Because there is little difference among AEDs in terms of efficacy, drug selection is often based on the adverse effects profile. AED toxicity is classified according to different parameters, such as severity, time of occurrence, organ system involvement, and mechanisms of action. Although most toxic reactions to drugs can be predicted from cumulative experience, prevention is not always possible, since multiple mechanisms and individual susceptibility to each drug participate in the final outcome. However, adverse effects can be reduced and appropriate action can be taken in time by means of a high degree of suspicion, knowledge of risk factors, and close follow-up. This article highlights factors to consider for detecting and managing AED adverse effects.

Neurotherapeutics, Jun 6, 2023

Frontiers in Neurology, Feb 14, 2023

Introduction: Pattern separation (PS) is a fundamental aspect of memory creation that defines the... more Introduction: Pattern separation (PS) is a fundamental aspect of memory creation that defines the ability to transform similar memory representations into distinct ones, so they do not overlap when storing and retrieving them. Experimental evidence in animal models and the study of other human pathologies have demonstrated the role of the hippocampus in PS, in particular of the dentate gyrus (DG) and CA. Patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HE) commonly report mnemonic deficits that have been associated with failures in PS. However, the link between these impairments and the integrity of the hippocampal subfields in these patients has not yet been determined. The aim of this work is to explore the association between the ability to perform mnemonic functions and the integrity of hippocampal CA , CA , and DG in patients with unilateral MTLE-HE. Method: To reach this goal we evaluated the memory of patients with an improved object mnemonic similarity test. We then analyzed the hippocampal complex structural and microstructural integrity using di usion weighted imaging. Results: Our results indicate that patients with unilateral MTLE-HE present alterations in both volume and microstructural properties at the level of the hippocampal subfields DG, CA , CA , and the subiculum, that sometimes depend on the lateralization of their epileptic focus. However, none of the specific changes was found to be directly related to the performance of the patients in a pattern separation task, which might indicate a contribution of various alterations to the mnemonic deficits or the key contribution of other structures to the function. Discussion: we established for the first time the alterations in both the volume and the microstructure at the level of the hippocampal subfields in a group of unilateral MTLE patients. We observed that these changes are greater in the DG and CA at the macrostructural level, and in CA and CA in the microstructural level. None of these changes had a direct relation to the performance of the patients in a pattern separation task, which suggests a contribution of various alterations to the loss of function.

Neuropediatrics, Oct 28, 2021

El presente documento de consenso se ha desarrollado con el objetivo de optimizar el tratamiento ... more El presente documento de consenso se ha desarrollado con el objetivo de optimizar el tratamiento de pacientes con crisis epilépticas (CE) en los ámbitos de urgencias prehospitalario y hospitalario. Un equipo multidisciplinar formado por urgenciólogos, neurólogos y neuropediatras de tres sociedades científicas,

Neuropediatrics, Oct 1, 2018

Epilepsy & Behavior, May 1, 2021

OBJECTIVE This study was aimed to analyze the effectiveness of sodium channel blockers (SCBs) in ... more OBJECTIVE This study was aimed to analyze the effectiveness of sodium channel blockers (SCBs) in CDKL5 deficiency disorder (CDD)-related epilepsy. METHODS A retrospective, observational study was performed, including patients with CDD diagnosis evaluated between 2016 and 2019 at three tertiary Epilepsy Centers. Demographic, electroclinical and genetic features, as well as ASM treatments and their outcomes were analyzed, with special focus on SCBs. RESULTS Twenty-one patients evaluated at three tertiary Epilepsy Centers were included, of which 19 presented with epilepsy (90.5%); all had pathogenic mutations of CDKL5. Six patients (31.6%) were classified as SCB responders (more than 50% reduction), four being currently seizure free (mean seizure-free period of 8 years). Most frequent SCB drugs were oxcarbazepine (OXC), carbamazepine (CBZ), and lacosamide (LCM). None of them presented relevant adverse events. In contrast, three patients showed seizure aggravation in the non-responder group. When comparing both groups, responders had statistically significant younger age at SCB treatment and epilepsy onset, higher proportion of focal epileptiform activity and less frequent history of West syndrome. CONCLUSIONS The results of this study indicate that treatment with SCBs might be effective and safe in a subset of patients with CDD-related epilepsy.

Frontiers in Neurology, Feb 17, 2022

This review aims to provide an updated perspective of epilepsy genetics and precision medicine in... more This review aims to provide an updated perspective of epilepsy genetics and precision medicine in adult patients, with special focus on developmental and epileptic encephalopathies (DEEs), covering relevant and controversial issues, such as defining candidates for genetic testing, which genetic tests to request and how to interpret them. A literature review was conducted, including findings in the discussion and recommendations. DEEs are wide and phenotypically heterogeneous electroclinical syndromes. They generally have a pediatric presentation, but patients frequently reach adulthood still undiagnosed. Identifying the etiology is essential, because there lies the key for precision medicine. Phenotypes modify according to age, and although deep phenotyping has allowed to outline certain entities, genotype-phenotype correlations are still poor, commonly leading to long-lasting diagnostic odysseys and ineffective therapies. Recent adult series show that the target patients to be identified for genetic testing are those with epilepsy and different risk factors. The clinician should take active part in the assessment of the pathogenicity of the variants detected, especially concerning variants of uncertain significance. An accurate diagnosis implies precision medicine, meaning genetic counseling, prognosis, possible future therapies, and a reduction of iatrogeny. Up to date, there are a few tens of gene mutations with additional concrete treatments, including those with restrictive/substitutive therapies, those with therapies modifying signaling pathways, and channelopathies, that are worth to be assessed in adults. Further research is needed regarding phenotyping of adult syndromes, early diagnosis, and the development of targeted therapies.

JAMA Neurology, Jun 1, 2022

IMPORTANCE New treatment options are needed for patients with Lennox-Gastaut syndrome (LGS), a pr... more IMPORTANCE New treatment options are needed for patients with Lennox-Gastaut syndrome (LGS), a profoundly impairing, treatment-resistant, developmental and epileptic encephalopathy. OBJECTIVE To evaluate the efficacy and safety of fenfluramine in patients with LGS. DESIGN, SETTING, AND PARTICIPANTS This multicenter, double-blind, placebo-controlled, parallel-group randomized clinical trial was conducted from November 27, 2017, to October 25, 2019, and had a 20-week trial duration. Patients were enrolled at 65 study sites in North America, Europe, and Australia. Included patients were aged 2 to 35 years with confirmed diagnosis of LGS and experienced 2 or more drop seizures per week during the 4-week baseline. Using a modified intent-to-treat method, data analysis was performed from

Neuropediatrics, Oct 28, 2021

Seizure-european Journal of Epilepsy, Jul 1, 2021

Clinical and Health, 1998

Las epilepsias fotosensibles con frecuencia tienen una base genética y se caracterizan por la pre... more Las epilepsias fotosensibles con frecuencia tienen una base genética y se caracterizan por la presencia de respuesta fotoparoxística y fotoconvulsiva, que puede ser detectada mediante estudios adecuados de electroencefalografía. Las formas de presentación y la severidad son muy variables, incluyendo personas completamente asintomáticas hasta enfermos con afectación severa del sistema nervioso central. En la mayoría de los casos es un trastorno relativamente benigno, en el cual el tratamiento y las medidas de prevención suelen ser eficaces.

Developmental Medicine & Child Neurology, Jan 26, 2022

AimTo investigate the short‐term efficacy and safety of high‐dose pyridoxine and pyridoxal 5‐phos... more AimTo investigate the short‐term efficacy and safety of high‐dose pyridoxine and pyridoxal 5‐phosphate (P5P) in the treatment of inherited glycosylphosphatidylinositol (GPI) deficiency‐associated epilepsy.MethodParticipants with genetically confirmed GPI deficiency were treated with oral pyridoxine or P5P as compassionate use in an agreed‐upon clinical regimen. Pyridoxine (20–30 mg/kg/day) was used for 3 months. Baseline evaluation included 4 weeks of prospective seizure data and one video electroencephalogram (EEG). Seizure frequency was captured daily. The EEG was repeated after reaching maximum dosage of pyridoxine. Pyridoxine was switched to P5P (20–30 mg/kg/day) if seizure burden was unchanged after 3 months' treatment. Another EEG was done after 3 months of P5P treatment. Primary outcome measures were reduction of seizure frequency and EEG improvements.ResultsSeven participants (one female, six males; age range 5–23 year; mean age 11 years 10 months, SD 5 year 2 months) were included. The genetic causes of inherited GPI deficiency were phosphatidylinositol N‐acetylglucosaminyltransferase subunit A/T/V deficiency. All had drug‐resistant epilepsy and neurodevelopmental impairment. We observed more than 50% seizure frequency reduction in 2 out of 7 and less than 50% reduction in another 3 out of 7 participants. No participants reached seizure freedom. No remarkable changes in electrophysiological findings were observed in 6 out of 7 participants treated with pyridoxine or P5P when comparing the baseline and follow‐up EEGs.InterpretationWe observed no long‐lasting electrophysiological improvements during treatment but pyridoxine may reduce seizure frequency or burden in inherited GPI deficiency.What this paper adds Inherited glycosylphosphatidylinositol (GPI) deficiency often causes early‐onset and drug‐resistant epilepsy. Vitamin B6 is a potential disease‐specific treatment; however, efficacy and safety are ill‐defined. Pyridoxine may reduce seizure frequency or burden in inherited GPI deficiency. Pyridoxine and P5P could prove to be a useful treatment in some individuals with inherited GPI deficiency and epilepsy.

Revista De Neurologia, 2000

What is pre-surgery evaluation? Surgery is one of the therapies to treat epilepsy. In order to de... more What is pre-surgery evaluation? Surgery is one of the therapies to treat epilepsy. In order to decide if surgery will be helpful for you, your doctor needs to evaluate the results from several medical tests. This handout describes several tests-your doctor will decide which of these tests are appropriate for you. You may not need all of these tests. After you complete the tests your doctor recommends, our specialists will review your case in our weekly Refractory Epilepsy Conference. All providers involved with your care review and discuss your test results and come up with a recommendation on the preferred treatment for your epilepsy. The entire evaluation process could take between 6 to 12 months, depending on the complexity of the case. Some of the tests require a hospital admission, and some are done in the outpatient clinic.

The redefinition of classical electroclinical syndromes and the emergence of neurogenetics has le... more The redefinition of classical electroclinical syndromes and the emergence of neurogenetics has led to a revolution in the field of developmental and epileptic encephalopathies (DEEs). In this context, advances in genetic techniques are leading to the final diagnosis of a large proportion of patients with DEE. However, up to 50% of patients with DEE remain undiagnosed. For patients with uncertain genetic etiology, there is a pressing need for the implementation of new targeted treatments and precision medicine. In some undiagnosed patients, genetic reanalysis with further in-depth or reverse phenotyping are valuable diagnostic tools to clarify new variants of uncertain significance. In other cases, the implementation of new bioinformatic algorithms is required for the update and reassessment of previously generated genetic data. Moreover, many other clinical tools have been developed for the management of patients of DEEs after a negative or inconclusive genetic testing. In this review, we highlight advances and limitations of new diagnostic strategies used in DEE patients without a known genetic etiology. Finally, we provide a wide perspective on aspects that will need further research, especially in non-Mendelian inheritance DEEs, such as those related to somatic mosaicism of the central nervous system or epigenetic and oligogenic mechanisms.

Neuropsychologia, Feb 1, 2021

Decades of research have increased the understanding of the contribution of the anterior temporal... more Decades of research have increased the understanding of the contribution of the anterior temporal lobes (ATLs) to semantic cognition. Nonetheless, whether semantic processing of different types of information show a selective relationship with left and right ATLs, or whether semantic processing in the ATLs is independent of the modality of the input is currently unknown. There exists evidence supporting each of these alternatives. A fundamental objection to these findings is that they were obtained from studies with patients with brain damage affecting extensive regions, sometimes bilaterally. In the current study, we assessed a group of 38 temporal lobe epilepsy (TLE) patients with either left or right small epileptogenic lesions with a battery of commonly used semantic tasks that tested verbal and non-verbal semantic processing. We found that left TLE patients exhibited worse performance than controls on the verbal semantic tasks, as expected, but also on the non-verbal semantic task. On the other hand, performance of the right TLE group did not differ from controls on the non-verbal task, but was worse on a semantic fluency task. When performance between patient groups was compared, we found that left TLE not only did worse than right TLE on the naming task, but also on the non-verbal associative memory task. When considered together, current data do not support a strong view of input modality differences between left and right ATLs. Additionally, they provide evidence indicating that the left and right ATLs do not make similar contributions to a singular functional system for semantic representation.

Developmental Medicine & Child Neurology, Jul 21, 2023

AimTo describe the experiences and unmet medical care needs of a group of parents of children wit... more AimTo describe the experiences and unmet medical care needs of a group of parents of children with developmental and epileptic encephalopathies (DEEs) caused by the SCN1A, KCNQ2, CDKL5, PCDH19, and GNAO1 variants.MethodA qualitative descriptive study was conducted. Participants were recruited using purposeful sampling. The inclusion criteria consisted of parents of children with DEEs caused by the SCN1A, KCNQ2, CDKL5, PCDH19, or GNAO1 variants, aged between 4 and 10 years old. In total, 21 parents were included. Data were acquired via researcher field notes and in‐depth interviews. A thematic analysis was performed.ResultsThree main themes were identified: (1) managing symptoms: epileptic seizures are experienced with great uncertainty and are accompanied by cognitive, behavioural, and motor symptoms; (2) accepting treatment: the ideal medication regimen is a challenge and the decision to withdraw or start a new therapy falls on the parents; and (3) therapeutic relationship and medical care: behaviours related to the health professional can hinder the therapeutic relationship with the parents. Parents are apprehensive about going to the emergency department.InterpretationProfessionals in emergency departments should acquire better knowledge of DEEs, welcome parents, and improve treatment for the children. The results of this study can serve as a starting point for a roadmap of relevant caregiver‐reported outcomes in DEEs, to be implemented with new clinical trials and aetiology‐targeted therapies.

Neurología, Mar 1, 2016

The use of the Multiphasic Personality Inventory Minnesota 2 (MMPI-2) for the diagnosis of psycho... more The use of the Multiphasic Personality Inventory Minnesota 2 (MMPI-2) for the diagnosis of psychogenic non-epileptic seizures (PNES) is controversial. This study examines the validity of the clinical scales and, unlike previous works, the content scales. Cross-sectional study of 209 patients treated in the epilepsy unit. We performed a logistic regression analysis, taking video-electroencephalography as the reference test, and predictor variables age, sex, IQ and clinical (model A) or content scales (model B) of the MMPI-2. The models were selected according to the Aikake index and compared using the DeLong test. We analyzed 37 patients with PNES alone, or combined with seizures, and 172 patients with seizures only. The model consisting of sex, Hs (hypochondriasis) and Pa (paranoia) showed a sensitivity of 77.1%, a specificity of 76.8%, a percentage of correct classification of 76.8%, and an area under the curve (AUC) of 0.836 for diagnosing CNEP. Model B, consisting of sex, HEA (health concerns) and FRS (fears), showed a sensitivity of 65.7%, a specificity of 78.0%, a percentage of correct classification of 75.9% and an UUC of 0.840. DeLong's test did not detect significant differences. The MMPI-2 has a moderate validity for the diagnosis of PNES in patients referred to an epilepsy unit. Using content scales does not significantly improve results from the clinical scales.

Seizure-european Journal of Epilepsy, Aug 1, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Seminars in Neurology, Jul 1, 2008

Adverse effects of antiepileptic drugs (AEDs) are considered by patients to be at least as import... more Adverse effects of antiepileptic drugs (AEDs) are considered by patients to be at least as important as repetitive seizures in terms of quality of life. AED toxicity is frequent and contributes to a high proportion of treatment failures. Despite its high prevalence and clinical relevance, screening for adverse reactions to AEDs is not systematically included in everyday clinical practice; therefore it is very likely that it remains underestimated. Because there is little difference among AEDs in terms of efficacy, drug selection is often based on the adverse effects profile. AED toxicity is classified according to different parameters, such as severity, time of occurrence, organ system involvement, and mechanisms of action. Although most toxic reactions to drugs can be predicted from cumulative experience, prevention is not always possible, since multiple mechanisms and individual susceptibility to each drug participate in the final outcome. However, adverse effects can be reduced and appropriate action can be taken in time by means of a high degree of suspicion, knowledge of risk factors, and close follow-up. This article highlights factors to consider for detecting and managing AED adverse effects.

Neurotherapeutics, Jun 6, 2023

Frontiers in Neurology, Feb 14, 2023

Introduction: Pattern separation (PS) is a fundamental aspect of memory creation that defines the... more Introduction: Pattern separation (PS) is a fundamental aspect of memory creation that defines the ability to transform similar memory representations into distinct ones, so they do not overlap when storing and retrieving them. Experimental evidence in animal models and the study of other human pathologies have demonstrated the role of the hippocampus in PS, in particular of the dentate gyrus (DG) and CA. Patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HE) commonly report mnemonic deficits that have been associated with failures in PS. However, the link between these impairments and the integrity of the hippocampal subfields in these patients has not yet been determined. The aim of this work is to explore the association between the ability to perform mnemonic functions and the integrity of hippocampal CA , CA , and DG in patients with unilateral MTLE-HE. Method: To reach this goal we evaluated the memory of patients with an improved object mnemonic similarity test. We then analyzed the hippocampal complex structural and microstructural integrity using di usion weighted imaging. Results: Our results indicate that patients with unilateral MTLE-HE present alterations in both volume and microstructural properties at the level of the hippocampal subfields DG, CA , CA , and the subiculum, that sometimes depend on the lateralization of their epileptic focus. However, none of the specific changes was found to be directly related to the performance of the patients in a pattern separation task, which might indicate a contribution of various alterations to the mnemonic deficits or the key contribution of other structures to the function. Discussion: we established for the first time the alterations in both the volume and the microstructure at the level of the hippocampal subfields in a group of unilateral MTLE patients. We observed that these changes are greater in the DG and CA at the macrostructural level, and in CA and CA in the microstructural level. None of these changes had a direct relation to the performance of the patients in a pattern separation task, which suggests a contribution of various alterations to the loss of function.

Neuropediatrics, Oct 28, 2021

El presente documento de consenso se ha desarrollado con el objetivo de optimizar el tratamiento ... more El presente documento de consenso se ha desarrollado con el objetivo de optimizar el tratamiento de pacientes con crisis epilépticas (CE) en los ámbitos de urgencias prehospitalario y hospitalario. Un equipo multidisciplinar formado por urgenciólogos, neurólogos y neuropediatras de tres sociedades científicas,

Neuropediatrics, Oct 1, 2018

Epilepsy & Behavior, May 1, 2021

OBJECTIVE This study was aimed to analyze the effectiveness of sodium channel blockers (SCBs) in ... more OBJECTIVE This study was aimed to analyze the effectiveness of sodium channel blockers (SCBs) in CDKL5 deficiency disorder (CDD)-related epilepsy. METHODS A retrospective, observational study was performed, including patients with CDD diagnosis evaluated between 2016 and 2019 at three tertiary Epilepsy Centers. Demographic, electroclinical and genetic features, as well as ASM treatments and their outcomes were analyzed, with special focus on SCBs. RESULTS Twenty-one patients evaluated at three tertiary Epilepsy Centers were included, of which 19 presented with epilepsy (90.5%); all had pathogenic mutations of CDKL5. Six patients (31.6%) were classified as SCB responders (more than 50% reduction), four being currently seizure free (mean seizure-free period of 8 years). Most frequent SCB drugs were oxcarbazepine (OXC), carbamazepine (CBZ), and lacosamide (LCM). None of them presented relevant adverse events. In contrast, three patients showed seizure aggravation in the non-responder group. When comparing both groups, responders had statistically significant younger age at SCB treatment and epilepsy onset, higher proportion of focal epileptiform activity and less frequent history of West syndrome. CONCLUSIONS The results of this study indicate that treatment with SCBs might be effective and safe in a subset of patients with CDD-related epilepsy.

Frontiers in Neurology, Feb 17, 2022

This review aims to provide an updated perspective of epilepsy genetics and precision medicine in... more This review aims to provide an updated perspective of epilepsy genetics and precision medicine in adult patients, with special focus on developmental and epileptic encephalopathies (DEEs), covering relevant and controversial issues, such as defining candidates for genetic testing, which genetic tests to request and how to interpret them. A literature review was conducted, including findings in the discussion and recommendations. DEEs are wide and phenotypically heterogeneous electroclinical syndromes. They generally have a pediatric presentation, but patients frequently reach adulthood still undiagnosed. Identifying the etiology is essential, because there lies the key for precision medicine. Phenotypes modify according to age, and although deep phenotyping has allowed to outline certain entities, genotype-phenotype correlations are still poor, commonly leading to long-lasting diagnostic odysseys and ineffective therapies. Recent adult series show that the target patients to be identified for genetic testing are those with epilepsy and different risk factors. The clinician should take active part in the assessment of the pathogenicity of the variants detected, especially concerning variants of uncertain significance. An accurate diagnosis implies precision medicine, meaning genetic counseling, prognosis, possible future therapies, and a reduction of iatrogeny. Up to date, there are a few tens of gene mutations with additional concrete treatments, including those with restrictive/substitutive therapies, those with therapies modifying signaling pathways, and channelopathies, that are worth to be assessed in adults. Further research is needed regarding phenotyping of adult syndromes, early diagnosis, and the development of targeted therapies.

JAMA Neurology, Jun 1, 2022

IMPORTANCE New treatment options are needed for patients with Lennox-Gastaut syndrome (LGS), a pr... more IMPORTANCE New treatment options are needed for patients with Lennox-Gastaut syndrome (LGS), a profoundly impairing, treatment-resistant, developmental and epileptic encephalopathy. OBJECTIVE To evaluate the efficacy and safety of fenfluramine in patients with LGS. DESIGN, SETTING, AND PARTICIPANTS This multicenter, double-blind, placebo-controlled, parallel-group randomized clinical trial was conducted from November 27, 2017, to October 25, 2019, and had a 20-week trial duration. Patients were enrolled at 65 study sites in North America, Europe, and Australia. Included patients were aged 2 to 35 years with confirmed diagnosis of LGS and experienced 2 or more drop seizures per week during the 4-week baseline. Using a modified intent-to-treat method, data analysis was performed from

Neuropediatrics, Oct 28, 2021

Seizure-european Journal of Epilepsy, Jul 1, 2021

Clinical and Health, 1998

Las epilepsias fotosensibles con frecuencia tienen una base genética y se caracterizan por la pre... more Las epilepsias fotosensibles con frecuencia tienen una base genética y se caracterizan por la presencia de respuesta fotoparoxística y fotoconvulsiva, que puede ser detectada mediante estudios adecuados de electroencefalografía. Las formas de presentación y la severidad son muy variables, incluyendo personas completamente asintomáticas hasta enfermos con afectación severa del sistema nervioso central. En la mayoría de los casos es un trastorno relativamente benigno, en el cual el tratamiento y las medidas de prevención suelen ser eficaces.

Developmental Medicine & Child Neurology, Jan 26, 2022

AimTo investigate the short‐term efficacy and safety of high‐dose pyridoxine and pyridoxal 5‐phos... more AimTo investigate the short‐term efficacy and safety of high‐dose pyridoxine and pyridoxal 5‐phosphate (P5P) in the treatment of inherited glycosylphosphatidylinositol (GPI) deficiency‐associated epilepsy.MethodParticipants with genetically confirmed GPI deficiency were treated with oral pyridoxine or P5P as compassionate use in an agreed‐upon clinical regimen. Pyridoxine (20–30 mg/kg/day) was used for 3 months. Baseline evaluation included 4 weeks of prospective seizure data and one video electroencephalogram (EEG). Seizure frequency was captured daily. The EEG was repeated after reaching maximum dosage of pyridoxine. Pyridoxine was switched to P5P (20–30 mg/kg/day) if seizure burden was unchanged after 3 months' treatment. Another EEG was done after 3 months of P5P treatment. Primary outcome measures were reduction of seizure frequency and EEG improvements.ResultsSeven participants (one female, six males; age range 5–23 year; mean age 11 years 10 months, SD 5 year 2 months) were included. The genetic causes of inherited GPI deficiency were phosphatidylinositol N‐acetylglucosaminyltransferase subunit A/T/V deficiency. All had drug‐resistant epilepsy and neurodevelopmental impairment. We observed more than 50% seizure frequency reduction in 2 out of 7 and less than 50% reduction in another 3 out of 7 participants. No participants reached seizure freedom. No remarkable changes in electrophysiological findings were observed in 6 out of 7 participants treated with pyridoxine or P5P when comparing the baseline and follow‐up EEGs.InterpretationWe observed no long‐lasting electrophysiological improvements during treatment but pyridoxine may reduce seizure frequency or burden in inherited GPI deficiency.What this paper adds Inherited glycosylphosphatidylinositol (GPI) deficiency often causes early‐onset and drug‐resistant epilepsy. Vitamin B6 is a potential disease‐specific treatment; however, efficacy and safety are ill‐defined. Pyridoxine may reduce seizure frequency or burden in inherited GPI deficiency. Pyridoxine and P5P could prove to be a useful treatment in some individuals with inherited GPI deficiency and epilepsy.

Revista De Neurologia, 2000

What is pre-surgery evaluation? Surgery is one of the therapies to treat epilepsy. In order to de... more What is pre-surgery evaluation? Surgery is one of the therapies to treat epilepsy. In order to decide if surgery will be helpful for you, your doctor needs to evaluate the results from several medical tests. This handout describes several tests-your doctor will decide which of these tests are appropriate for you. You may not need all of these tests. After you complete the tests your doctor recommends, our specialists will review your case in our weekly Refractory Epilepsy Conference. All providers involved with your care review and discuss your test results and come up with a recommendation on the preferred treatment for your epilepsy. The entire evaluation process could take between 6 to 12 months, depending on the complexity of the case. Some of the tests require a hospital admission, and some are done in the outpatient clinic.