Jose Luis López-Sendón Moreno

Hospital Universitario Ramón y Cajal · Departamento de Neurología

Huntington’s disease (HD) is a neurodegenerative disease for which there is no curative treatment available. Given that the endocannabinoid system is involved in the pathogenesis of HD mouse models, stimulation of specific targets within this signaling system has been investigated as a promising therapeutic agent in HD. We conducted a double-blind,...

Introduction Response to drug withdrawal in patients with suspected drug-induced parkinsonism (DIP) is of prognostic and therapeutic importance, but cannot be predicted solely on clinical information. The aim of this study was to validate SN hyperechogenicity (SN+) assessed by transcranial sonography as a predictor of response to drug withdrawal in...

Huntington's disease (HD) is a neurodegenerative disease caused by a cytosine adenosine guanine (CAG) expansion in the huntingtin gene. The length of the triplet repeat is the most important factor in determining age of onset and the severity of the disease, but substantial variability of these parameters is attributed to other factors. To investig...

Drug-induced parkinsonism (DIP) has been claimed to be the most prevalent cause of secondary parkinsonism in clinical practice in the Western world. Since the first descriptions in the early 1950s the prevalence of DIP seems to be increasing and approaching that of idiopathic Parkinson’s disease (iPD) due to the aging of the population and the risi...

Limited information is available on patients' experience living with Huntington’s disease (HD). The primary objective of this study was to assess the health-related quality of life and well being of patients with HD. A non-interventional, cross-sectional study was conducted in 17 hospitals-based movement disorders units in Spain. Patients aged ≥ 18...

Metformin is a widely prescribed drug to treat type 2 diabetes worldwide. This is a pleiotropic drug, that activates a range of targets, among which is AMP-activated protein kinase (AMPK). This enzyme is an activator of autophagy, which is one of the key pathways of misfolded protein clearance. From work done in the lab, in silico (analysis of Enro...

Most patients with Parkinson's disease experience motor fluctuations or 'off' periods, which impact on their daily activities, increase their disability and diminish their quality of life. They suffer from these fluctuations despite multiple adjustments to the schedules, doses and intake of medication. In this context, on-demand or rescue treatment...

Background and purpose: The aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. Methods: We conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders U...

Background: SARS-CoV-2 infection potentiates thromboinflammation contributing to poor outcomes in COVID-19. In non-critically ill patients hospitalized for COVID-19, therapeutic-dose heparin improves clinical outcomes. We hypothesized therapeutic-dose heparin impacts thromboinflammatory biomarkers in patients hospitalized for COVID-19 infection. Me...

Background: Post-acute sequela of COVID-19 (PASC) is a complication of SARS-CoV-2 causing persistent symptoms and impaired functional status. We studied the effect of P2Y12 inhibitors on health-related Quality of Life (QoL) at 90 days in critically ill patients hospitalized for COVID-19. Methods: Adults hospitalized for COVID-19 who were randomized...

Background Progressive cognitive decline is an inevitable feature of Huntington’s disease (HD) but specific criteria and instruments are still insufficiently developed to reliably classify patients into categories of cognitive severity and to monitor the progression of cognitive impairment. Methods We collected data from a cohort of 180 positive g...

Introduction: Functional neurological disorders (FND) are a frequent reason for visits in neurology. However, specific training on these disorders during undergraduate and residency training is limited. This study assesses the knowledge, attitude and exposure of medical students to FNDs before completing their medical degree. Patients and methods...

Background Cannabinoids have been suggested to alleviate frequently experienced symptoms of reduced mental well-being such as anxiety and depression. Mental well-being is an important subdomain of health-related quality of life (HRQoL). Reducing symptoms and maintaining HRQoL are particularly important in malignant primary brain tumor patients, as...

Background Previous studies linked disease-progression variables such as age at onset or survival to both genetic, and non-genetic factors in Parkinson's disease (PD) patients. Objective The aim of this study was to assess how genetic and non genetic factors act as modifiers of age at onset and survival and in a cohort of 753 PD patients, and to d...

Importance Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19. Objective To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non–critically ill patients hospitalized for COVID-19. Design, Setting, and Participants An open-label, bayesian, adaptive r...

Parkinson’s disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson’s disease....

Background Parkinson’s disease (PD) is a neurodegenerative movement disorder affecting 1–5% of the general population for which neither effective cure nor early diagnostic tools are available that could tackle the pathology in the early phase. Here we report a multi-stage procedure to identify candidate genes likely involved in the etiopathogenesis...

Background: Clinical diagnosis of atypical parkinsonisms may be challenging. The eye-of-the-tiger sign on brain MRI, typical of neurodegeneration with brain iron accumulation, has been anecdotally observed in cases clinically diagnosed as atypical parkinsonisms. Objectives: To show how clinical syndromes and even neuroimaging sometimes may lead...

Background: Arithmetic word-problem solving depends on the interaction of several cognitive processes that may be affected early in the disease in gene-mutation carriers for Huntington's disease (HD). Objective: Our goal was to examine the pattern of performance of arithmetic tasks in premanifest and manifest HD, and to examine correlations betw...

Huntington’s disease (HD) is a hereditary neurodegenerative disorder of the basal ganglia for which disease-modifying treatments are not yet available. Although gene-silencing therapies are currently being tested, further molecular mechanisms must be explored to identify druggable targets for HD. Cytoplasmic polyadenylation element binding proteins...

BACKGROUND Gliomas are primary brain tumors with a dismal prognosis. Reducing symptoms and maintaining quality of life (QoL) are main treatment aims in glioma patients. Mental well-being is an important subdomain of QoL. Cannabinoids have been suggested to alleviate frequently experienced symptoms of reduced mental well-being such as anxiety or dep...

Background Although promising gene-silencing therapies are being tested for Huntington’s disease (HD), no disease-modifying treatments are available. Thus, study of molecular mechanisms underneath Htt-mutation must continue to identify easily druggable targets. Cytoplasmic polyadenylation element binding proteins 1–4 (CPEB1–4) are RNA-binding prote...

Background and purpose The aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. Methods We conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders Unit,...

Introduction Parkinson’s disease (PD) is more frequent in the elderly and increases the risk of respiratory infections. Previous data on PD and SARS-CoV-2 are scarce, suggesting a poor prognosis in advanced disease and second-line therapies. Methods A retrospective case–control study comparing patients with PD and COVID-19 and patients with PD wit...

Background Parkinson’s disease (PD) is a neurodegenerative movement disorder affecting 1–5% of the general population for which neither effective cure nor early diagnostic tools are available that could tackle the pathology in the early phase. Here we report a multi-stage procedure to identify candidate genes likely involved in the etiopathogenesis...

Background Thrombo-inflammation may contribute to morbidity and mortality in Covid-19. We hypothesized that therapeutic-dose anticoagulation may improve outcomes in non-critically ill patients hospitalized for Covid-19. Methods In an open-label adaptive multiplatform randomized controlled trial, non-critically ill patients hospitalized for Covid-19...

OBJECTIVE: Parkinson's disease (PD) is a complex neurodegenerative disorder. Males are on average ~ 1.5 times more likely to develop PD compared to females with European ancestry. Over the years genome-wide association studies (GWAS) have identified numerous genetic risk factors for PD, however it is unclear whether genetics contribute to disease e...

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...

The original version of this article unfortunately contained a mistake.

Importance Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased risk of disease. Improved understanding of the underlying genes and mechanisms at these loci will be key to understanding the pathogenesis of PD. Objectiv...

Importance Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased risk of disease. Improved understanding of the underlying genes and mechanisms at these loci will be key to understanding the pathogenesis of PD. / Objecti...

Background: Urinary symptoms are common, disabling and generally unresponsive to treatment in Parkinson´s disease (PD). Safinamide is approved as an add-on therapy to levodopa to improve fluctuations. Methods: Retrospective analysis of electronic records of nondemented PD patients seen consecutively in a Movement Disorders Unit (November 2018-Fe...

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...

View Supplementary Video 1 View Supplementary Video 2

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...

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...

Background Cognitive impairment is an essential feature of Huntington’s disease (HD) and dementia is a predictable outcome in all patients. However, validated instruments to assess global cognitive performance in the field of HD are lacking.Objectives We aimed to explore the utility of the Parkinson’s disease-Cognitive Rating Scale (PD-CRS) for the...

KCNJ10 encodes the inward-rectifying potassium channel (Kir4.1) that is expressed in the brain, inner ear, and kidney. Loss-of-function mutations in KCNJ10 gene cause a complex syndrome consisting of epilepsy, ataxia, intellectual disability, sensorineural deafness, and tubulopathy (EAST/SeSAME syndrome). Patients with EAST/SeSAME syndrome display...

Background: The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases. Objectives: To perform the largest PD genome-wide association study restricted to a single country. Methods: We performed a GWAS f...

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...

Background: The Iberian peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases. Objectives: To perform the largest Parkinson disease (PD) genome-wide association study (GWAS) restricted to a single country. Methods:...

Background: The frequency of late-onset Huntington's disease (>59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients fr...

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...

Drug-induced parkinsonism (DIP) and tardive dyskinesia (TD) are iatrogenic consequences of antidopaminergic drugs. Both are particularly prevalent among the elderly and those with dementia. However, despite their prevalence, these disorders are often overlooked. Both entities share risk factors, physiopathological mechanisms and, to some degree, th...

Neurofilament light proteins (NFL) are a structural element of the neuronal cytoskeleton and are released with neuronal damage. Its levels are increased in cerebrospinal fluid (CSF) in the setting of neurodegenerative diseases. We investigated the CSF-NFL levels of Huntington´s disease (HD) patients (participating in a clinical trial SAT-HD) as wel...

Botulinum toxin type A is one of the most useful treatments of sialorrhea in neurological disorders. Evidence for the use of incobotulinumtoxin A (inco-A) in the treatment of sialorrhea is limited. Thirty-six patients with sialorrhea were treated with infiltrations of inco-A into both parotid glands. The severity of sialorrhea was evaluated by the...

INTRODUCCION: La problemática de los trastornos del movimiento (TM) es compleja y la duración y frecuencia de las consultas presenciales puede estar limitada por problemas de espacio y tiempo. Analizamos el funcionamiento de un servicio de atención por correo electrónico institucional para médicos de Atención Primaria (MAP) y pacientes en la Unidad...

Introduction The clinical problems of patients with movement disorders (MD) are complex, and the duration and frequency of face-to-face consultations may be insufficient to meet their needs. We analysed the implementation of an e-mail-based query service for our MD unit's patients and their primary care physicians (PCPs). Methods We retrospectivel...

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify...

Background: In Huntington's Disease (HD) cognitive decline can occur before unequivocal motor signs become apparent. As cognitive decline often starts early in the course of the disease and has a progressive nature over time, cognition can be regarded as a key target for symptomatic treatment. The specific progressive profile of cognitive decline...

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify...

Background Rating movement disorders is at best semiquantitative and highly subjective. Aims To provide an objective and quantitive method for measurement of movement disorders. Methods Patients and controls were videotaped under standard conditions with smart phones equiped with Android systems and with programs obtained from Mementum, a softwar...

Background We conducted a pilot trial to assess the safety and tolerability of Sativex in HD (SAT-HD). Several biomarkers were studied in order to detect putative sub-clinical molecular effects of cannabinoids. Aims Here we present the results of the CSF analysis, as indicated in the protocol, of all the twenty four patients who underwent the two...

A prospective, observational multicenter study was carried out assessing neuropsychiatric symptoms in a sample of 117 subjects in order to validate the Spanish version of the Problem Behaviors Assessment-Short (PBA-s). The psychometric properties of this version were analyzed. Inter- and intra-rater reliability were good: the mean weighted Cohen's...

Introduction: The clinical problems of patients with movement disorders (MD) are complex, and the duration and frequency of face-to-face consultations may be insufficient to meet their needs. We analysed the implementation of an e-mail-based query service for our MD unit's patients and their primary care physicians (PCPs). Methods: We retrospect...

Introduction: Huntington’s disease (HD) is an autosomal dominant fully penetrant and fatal disorder caused by a CAG (glutamine) trinucleotide expansion in the huntingtin (htt) gene. To the date, there is no established disease-modifying treatment and the symptomatic therapies are limited. Recent advances in the understanding of HD pathology, natura...

Abstract Background There is a great interest in developing simple, user friendly and inexpensive tools for quantification and elucidation of motor deficits in Parkinson's disease (PD). These systems could help to monitor the clinical status of patients with PD, to develop better treatments and to identify subjects with subtle motor signs that mig...

Hyperechogenicity of the substantia nigra on transcranial sonography is used for diagnosing Parkinson disease (PD). Cutoff values for the substantia nigra echogenic area, defining substantia nigra hyperechogenicity, vary among ultrasound systems from different manufacturers. In this study we wanted to determine the cutoff criterion for a Toshiba (T...

Objetivos: Neurodegeneración por acumulación cerebral de hierro tipo 2 (NBIA2) es una enfermedad rara producida por una mutación en el gen PLA2G6 que produce un amplio espectro de manifestaciones clínicas y puede presentarse a distintas edades, lo que en ocasiones causa retraso en el diagnóstico. Presentamos el caso de dos hermanas afectadas de NBI...

In this work we investigate the role of CHIP in a new CHIP-mutation related ataxia and the therapeutic potential of trehalose. The patient's fibroblasts with a new form of hereditary ataxia, related to STUB1 gene (CHIP) mutations, and three age and sex-matched controls were treated with epoxomicin and trehalose. The effects on cell death, protein m...

Introduction Light subunit of neurofilament protein (NFL) is a structural element of neurons. Its levels are increased in cerebrospinal fluid (CSF) in the setting of neurological diseases, including Huntington’s disease (HD), and are considered a marker of neuronal damage. HD is a paradigm of neurodegeneration in the need of appropriate biomarkers....

The new diagnostic criteria for Alzheimer's disease (AD) include brain imaging and cerebrospinal fluid (CSF) biomarkers, with the aim of increasing the certainty of whether a patient has an ongoing AD neuropathologic process or not. Three CSF biomarkers, Aß42, total tau, and phosphorylated tau, reflect the core pathological features of AD. It is al...

Huntington's disease (HD) is a neurodegenerative disorder characterized by progressive motor, cognitive and psychiatric deficits, associated with predominant loss of striatal neurons and is caused by polyglutamine expansion in the huntingtin protein. Mutant huntingtin protein and its fragments are resistant to protein degradation and produce a bloc...