Rafael Toledano

Rafael Toledano
Hospital Ruber Internacional

MD

About

77
Publications
14,113
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1,446
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Introduction
Rafael Toledano currently works at the Department of Neurology, Hospital Ruber Internacional and Hospital Ramón y Cajal. Rafael does research in Epilepsy.

Publications

Publications (77)
Article
Full-text available
SCN8A‐developmental and epileptic encephalopathy is caused by mutations in the SCN8A gene encoding the Nav1.6 sodium channel, and is characterized by intractable multivariate seizures and developmental regression. Fenfluramine is a repurposed drug with proven antiseizure efficacy in Dravet syndrome and Lennox‐Gastaut syndrome. The effect of fenflur...
Article
Purpose There is scarce evidence of effective treatments for the chronic phase of Febrile infection-related epilepsy syndrome (FIRES). This study aimed to analyze the outcomes of treatment with anakinra and tocilizumab. Methods Retrospective study including patients receiving either anti-interleukin-1 (anti-IL-1, anakinra) or anti-IL-6 (tocilizuma...
Article
Full-text available
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 literatu...
Article
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Malformations of cortical development (MCD) comprise a broad spectrum of structural brain lesions frequently associated with epilepsy. Disease definition and diagnosis remain challenging and are often prone to arbitrary judgment. Molecular classification of histopathological entities may help rationalize the diagnostic process. We present a retrosp...
Article
Introduction: Perampanel (PER) is an antiepileptic drug approved in Europe as add-on therapy for patients with focal onset seizures (with or without secondary generalisation) from the age of 4 years, and for primary generalised tonic-clonic seizures from 7 years of age. Objective: Review current evidence on treatment with PER monotherapy after conv...
Preprint
Full-text available
Memory for aversive events is central to survival, but can also become maladaptive in psychiatric disorders. Emotional memory relies on the amygdala and hippocampus, but the neural dynamics of their communication during emotional memory encoding remain unknown. Using simultaneous intracranial recordings from both structures in human patients, we sh...
Article
Full-text available
Purpose: We hypothesized that epilepsy associated with temporal pole encephaloceles (ETPE) could be the consequence and an unrecognized manifestation of idiopathic intracranial hypertension (IIH). To test this hypothesis in patients with ETPEs we evaluated: 1) the frequency of two radiological signs of IIH and 2) whether these patients develop over...
Article
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...
Article
Full-text available
Objective Stereoelectroencephalography (SEEG) is a technique for preoperative evaluation of patients with difficult-to-localise refractory focal epilepsy (DLRFE), enabling the study of deep cortical structures. The procedure, which is increasingly used in international epilepsy centres, has not been fully developed in Spain. We describe our experie...
Article
Full-text available
Despite the increasing evidence of the benefit of corticosteroids for the treatment of moderate-severe coronavirus disease 2019 (COVID-19) patients, no data are available about the potential role of high doses of steroids for these patients. We evaluated the mortality, the risk of need for mechanical ventilation (MV), or death and the risk of devel...
Article
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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...
Article
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 inpu...
Article
The role of immunosuppression among coronavirus disease 2019 (COVID‐19) patients has not been elucidated and management may be challenging. This observational study included confirmed COVID‐19 patients. The primary endpoint was the development of moderate–severe acute respiratory distress syndrome (ARDS). Time to moderate–severe ARDS, the need for...
Article
Objective To develop and validate an epilepsy-specific scale for comprehensive functional assessment of patients with epilepsy, named Epidaily. Methods The multidisciplinary research group created through brainstorming a list of 47 items to explore the cognitive, social, basic and instrumental functionality of the patient. A group of epilepsy expe...
Article
Full-text available
A 24-year-old woman with refractory focal epilepsy was evaluated for epilepsy surgery. MRI showed an extensive malformation of cortical development (MCD) that involved the right perisilvian region and compromised the motor gyrus (figure 1). Functional MRI showed an abnormal location of the motor function with anterior displacement of the pyramidal...
Article
Background Surgery is a widely accepted treatment option for drug-resistant focal epilepsy. A detailed analysis of longitudinal postoperative seizure outcomes and use of antiepileptic drugs for different brain lesions causing epilepsy is not available. We aimed to analyse the association between histopathology and seizure outcome and drug freedom u...
Article
Herpes simplex virus (HSV) encephalitis is the most common sporadic viral encephalitis and has been associated with refractory epilepsy. The detection of HSV-DNA in the brain parenchyma along with the inflammatory features of the pathology before the patient developed symptoms supports the presence of a chronic encephalitis confined to the temporal...
Article
Objective: To assess the effectiveness and tolerability of perampanel (PER) monotherapy in routine clinical practice for the treatment of focal onset and generalized tonic-clonic seizures (GTCS). Methods: This multicenter, retrospective, observational study was conducted in patients aged ≥12 years treated with PER as primary monotherapy or conve...
Article
Full-text available
The COVID-19 pandemic represents an unprecedented international crisis with significant health, economic, and social consequences. This scenario has forced the medical community to face new practical and ethical challenges that require rapid responses. Early data show a variety of neurological manifestations in a significant proportion of patients...
Preprint
Full-text available
BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has spread rapidly worldwide. The role of immunosuppression among COVID-19 patients has not been elucidated and management may be challenging. OBJECTIVE: To assess differences in severe outcomes of hospitalized patients with COVID-19 according to immune system st...
Book
Full-text available
El presente Manual de Práctica Clínica en Epilepsia tiene por objeto ayudar al clínico y a los pacientes en la toma de decisiones en situaciones clínicas concretas, se fundamenta en las mejores evidencias científicas posibles y en la experiencia de los autores, sobre los aspectos diagnósticos, clasificatorios, terapéuticos, y pronósticos relacionad...
Preprint
Full-text available
BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has spread rapidly worldwide. The role of immunosuppression among COVID-19 patients has not been elucidated and management may be challenging. OBJECTIVE: To assess differences in severe outcomes of hospitalized patients with COVID-19 according to immune system s...
Article
Mesial temporal lobe epilepsy (mTLE) is a neurological disorder associated with histopathological changes in different subfields of the hippocampus. These alterations have been associated with memory difficulties. In this study, we tested the hypothesis that these difficulties stem on mnemonic discrimination impairment due to a reduced ability to m...
Poster
Full-text available
Rationale: Perampanel (PER) is an antiepileptic drug (AED) initially approved as adjunctive therapy of focal seizures with or without secondary generalization and primary generalized tonic-clonic seizures. It has recently been approved as monotherapy in focal seizures only in the USA. It has shown better efficacy and tolerability when used as early...
Article
Introduction: Substantia nigra hyperechogenicity (SN+) in transcranial sonography (TCS) is frequent in Parkinson's disease (PD), while lenticular nucleus hyperechogenicity (LN+) and 3rd ventricle enlargement (3V+) are typical of Atypical Parkinsonisms (AP). However, there are no studies assessing the diagnostic yield of all TCS biomarkers in the t...
Article
Background: Patients' education is the most relevant contributor to patient self-management of epilepsy. We aimed to assess the acquisition of knowledge after a semi-structured interview. Methods: We performed a quasi-experimental prospective study with a cohort of patients with epilepsy admitted for prolonged video electroencephalogram (VEEG)....
Article
Full-text available
Objective: Stereoelectroencephalography (SEEG) is a technique for preoperative evaluation of patients with difficult-to-localize refractory focal epilepsy (DLRFE), enabling the study of deep cortical structures. The procedure, which is increasingly used in international epilepsy centres, has not been fully developed in Spain. We describe our experi...
Article
Visual object naming is a complex cognitive process that engages an interconnected network of cortical regions moving from occipitotemporal to anterior–inferior temporal cortices, and extending into the inferior frontal cortex. Naming can fail for diverse reasons, and different stages of the naming multi‐step process appear to be reliant upon the i...
Article
Full-text available
Several lines of research have linked olfactory regions with the pathophysiology of focal epilepsies. Among those regions, the piriform cortex represents the major part of the primary olfactory cortex. According to this data, we raised the hypothesis that in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis exists an...
Article
Full-text available
Idiopathic photosensitive occipital lobe epilepsy (IPOE) is a syndrome that should be suspected in patients with seizures with occipital semiology, photosensitivity, and normal MRI. It should be distinguished from occipital epilepsy of unknown aetiology (cryptogenic) given the differences in management. We reviewed patients with occipital seizures...
Article
Full-text available
Objectives Substantia nigra hyperechogenicity (SN+) detected by transcranial ultrasound (TUS) is useful for Parkinson’s disease (PD) diagnosis. Approximately 15% false negative results of unknown significance are reported. However, most TUS studies are transversal, and diagnosis of PD may change during follow-up. Methods Analysis of our prospectiv...
Article
Full-text available
Objectives Perampanel is an antiepileptic drug (AED) approved for add‐on treatment of focal seizures (with or without generalization) and primary generalized tonic‐clonic (GTC) seizures. Our objective was to explore the effectiveness and tolerability of adjunctive perampanel in patients with drug‐resistant myoclonic seizures, after failure of other...
Article
Background: Ring chromosome 20 (R20) syndrome is a chromosomal disorder characterized mainly by drug-resistant frontal lobe seizures, recurrent nonconvulsive status epilepticus (NCSE), and typical EEG features. The aim of this study was to investigate if this triad is common and specific to all patients with R20. Methods: In this cross-sectional...
Article
Epilepsy is a global disease with an unequal distribution. About 80% of the affected individuals reside in low and middle income countries. The incidence and prevalence of epilepsy in low income populations is higher than in the rest of the world, this is partly explained by some risk factors such as head trauma, perinatal injury and CNS infections...
Article
Full-text available
Aphasic status epilepticus is an uncommon entity that should be included in the differential diagnosis of persistent and sudden language disorders. In our study, we describe seven patients admitted with clinical and electroencephalographic diagnosis of aphasic status, who were studied with both neuroimaging and electroencephalogram. The mean age wa...
Article
Full-text available
Background Detailed neuropathological information on the structural brain lesions underlying seizures is valuable for understanding drug-resistant focal epilepsy. Methods We report the diagnoses made on the basis of resected brain specimens from 9523 patients who underwent epilepsy surgery for drug-resistant seizures in 36 centers from 12 European...
Poster
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Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Frontal Lobe Epilepsy (MOGHE) is a recently described clinico-pathological entity associated with a drug-resistant epilepsy. In this communication we report the clinical and prognostic features of patients with MOGHE in our clinic. Out of 33 patients with focal cortical...
Article
Eslicarbazepine acetate (ESL, Aptiom™) is a once-daily anticonvulsant, approved as adjunctive treatment of partial-onset seizures (POS). Historical-controlled trials investigating the use of ESL as monotherapy have demonstrated a favorable efficacy and tolerability profile in patients with POS. This prospective, non-interventional study recruited P...
Article
Full-text available
Highlights • 7 of 9 patients with GGE reduced ≥ 50% their tonic–clonic seizure frequency on LCM. • All 7 patients remained seizure free for > 1 year, and 2 of them for > 5 years. • In 2 of the 9 patients, both with Juvenile Absence Epilepsy, absences aggravated. • One aggravation consisted on a myoclonia and absence status, in a patient with no his...
Article
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Background and purpose: We aimed to determine the correlation between subjective evaluations of mood and cognitive functions by patients and informants, and the findings of a battery of neuropsychological tests. Methods: We analyzed 74 subjects recruited from a general neurology clinic, comprising 37 patients with cognitive complaints and 37 inf...
Article
A 56-year-old man presented with a 1-month history of daily autonomic seizures (tachycardia, diaphoresis, and nausea). Diagnosis of limbic encephalitis was confirmed based on brain MRI findings and anti-LGI1 antibodies found in CSF. Autonomic status epilepticus was diagnosed on a video-EEG study, while arterial spin labeling (ASL) sequences and ¹⁸F...
Article
Full-text available
A fast, subcortical pathway to the amygdala is thought to have evolved to enable rapid detection of threat. This pathway's existence is fundamental for understanding nonconscious emotional responses, but has been challenged as a result of a lack of evidence for short-latency fear-related responses in primate amygdala, including humans. We recorded...
Article
Objective: Small temporal pole encephalocele (STPE) can be the pathologic substrate of epilepsy in a subgroup of patients with noninformative magnetic resonance imaging (MRI). Herein, we analyzed the clinical, neurophysiologic, and radiologic features of the epilepsy found in 22 patients with STPE, and the frequency of STPE in patients with refrac...
Article
Objective: Naming difficulties are frequently observed in patients with temporal lobe epilepsy (TLE). Although damage/removal of regions of the anterior temporal neocortex including the temporal pole is considered critical for those difficulties, 1 relevant hypothesis proposes that hippocampal damage also has a role. Our aim was to better understa...
Article
The histopathological spectrum of human epileptogenic brain lesions is widespread including common and rare variants of cortical malformations. However, 2 - 26% of epilepsy surgery specimens are histopathologically classified as non-lesional. We hypothesized that these specimens include also new diagnostic entities, in particular when presurgical m...
Article
Generalized Fixation-off Sensitivity (CGE-FoS) patients present abnormal EEG patterns when losing fixation. In the present work, we studied two CGE-FoS epileptic patients with simultaneous EEG-fMRI. We aim to identify brain areas that are specifically related to the pathology by identifying the brain networks that are related to the EEG brain alter...
Article
The goal of this study is to report the efficacy and tolerability of lacosamide (LCM) monotherapy, as first-line and conversion regimens, in the treatment of patients with partial-onset seizures. We retrospectively reviewed the charts of patients with focal epilepsy on LCM monotherapy from six centers in Spain. Efficacy and tolerability were evalua...
Article
Full-text available
Naming is considered a left hemisphere function that operates according to a posterior-anterior specificity gradient, with more fine-grained information processed in most anterior regions of the temporal lobe (ATL), including the temporal pole (TP). Word finding difficulties are typically assessed using visual confrontation naming tasks, and have b...
Article
Background: The validity of neuropsychological tests for the differential diagnosis of degenerative dementias may depend on the clinical context. We constructed a series of logistic models taking into account this factor. Methods: We retrospectively analyzed the demographic and neuropsychological data of 301 patients with probable Alzheimer's di...
Article
Full-text available
Introduction 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. Methods Cross-sectional study of 209 patients treated in the epilepsy unit. We pe...
Article
Full-text available
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 reg...
Article
Full-text available
An increasing amount of evidence supports a crucial role for the anterior temporal lobe (ATL) in semantic processing. Critically, a selective disruption of the functional connectivity between left and right ATLs in patients with chronic aphasic stroke has been illustrated. The aim of the current study was to evaluate the consequences that lesions o...
Article
Full-text available
Mesial temporal lobe epilepsy (mTLE) is the most prevalent form of focal epilepsy, and hippocampal sclerosis (HS) is considered the most frequent associated pathological finding. Recent connectivity studies have shown that abnormalities, either structural or functional, are not confined to the affected hippocampus, but can be found in other connect...
Article
Objective To analyze the usefulness of a specific EEG activation protocol during video-EEG (VEEG) monitoring in the differential diagnosis of epilepsy. Method Since January 2009, 181 patients underwent two different EEG activation protocols during VEEG monitoring in the Epilepsy Unit of Hospital Ruber International. One protocol (the “standard pro...
Article
This retrospective study reports the early experience with lacosamide (LCM) as adjunctive therapy in Spanish patients with refractory focal epilepsy. Sixty patients (mean age 38.3 years, 54% women, mean epilepsy duration 27.2 years, mean seizure rate 9.7/month, and 28% with mainly nocturnal seizures) taking ≥2 antiepileptic drugs (mean 2.2) were in...
Article
Full-text available
current diagnostic criteria of probable Creutzfeldt-Jakob disease (CJD) include a combination of clinical, EEG and analytic data. Recent data indicate that brain MRI including fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) sequences can be a valid and reliable tool for the diagnosis of CJD. We describe our experien...
Article
The main feature of akinetic seizures is the inhibition of voluntary movements without impairment of awareness. Most clinical information about akinetic seizures has been obtained from cortical electrical stimulation studies, whereas clinical and video-electroen-cephalography (EEG) features have not been described thoroughly. We aimed to analyze cl...
Article
Full-text available
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 systematicall...