Jaime Kulisevsky

Jaime Kulisevsky
Hospital de la Santa Creu i Sant Pau · Neurology Services

MD,PhD

About

518
Publications
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Publications

Publications (518)
Article
Full-text available
Extracellular vesicles (EVs) in cerebrospinal fluid (CSF) represent a valuable source of biomarkers for central nervous system (CNS) diseases, offering new pathways for diagnosis and monitoring. However, existing methods for isolating EVs from CSF often prove to be labor-intensive and reliant on specialized equipment, hindering their clinical appli...
Article
Full-text available
Background/Objectives: The treatment of tics and psychiatric comorbidities is crucial when they affect the patient’s well-being and relationships. However, the optimal pharmacological treatment (PT) tailored to each patient’s phenotype remains unclear. The primary objective of this study is to describe the clinical characteristics and treatment rec...
Article
Full-text available
Despite the advances in the understanding of Huntington's disease (HD), there is a need for molecular biomarkers to categorize mutation carriers during the preclinical stage of the disease preceding functional decline. Small RNAs (sRNAs) are a promising source of biomarkers since their expression levels are highly sensitive to pathobiological proce...
Conference Paper
Background Clinical diagnosis of Huntington’s disease (HD) relies on motor symptoms, but premanifest carriers show brain imaging and cognitive changes decades earlier. In this context, identifying early biomarkers is crucial. Extracellular small RNAs (sRNAs) are promising biomarkers due to their sensitivity to pathobiological processes. Easily foun...
Conference Paper
Background The brain systems involved in encoding reward-related signals and in reward prediction are compromised in Huntington’s disease (HD). Few studies have explored the integrity of these processes and their impact on behavior. Methods 49 gene mutation carriers (preHD: n=21; HD: n=28) and 21 controls were recruited. We designed a decision-mak...
Conference Paper
Background Recent studies have shown abnormal tau accumulation in the brains of Huntington's disease (HD) patients, highlighting tau protein dysregulation as a key aspect of its pathogenesis. Particularly, the role of 4R tau isoforms has been connected to HD progression and cognitive decline. Although tau protein levels have been examined in cerebr...
Conference Paper
Objective This study aims to investigate correlations between mHtt and NfL levels and MRI findings in individuals at different stages of HD, including presymptomatic and symptomatic individuals. Background Biomarkers in Huntington's disease (HD) are crucial for understanding disease progression and developing effective therapies. Cerebrospinal flu...
Conference Paper
Background Impairment of the endosomal/lysosomal system is present in HD. Indeed, we previously described reduced levels of Alix, a protein associated with this system and neuronal death, in postmortem HD brains. Aims Here, we investigated whether alterations in Alix protein levels could be detected in cerebrospinal fluid (CSF) of HD mutation carr...
Conference Paper
Background In Huntington’s disease (HD), language disturbances have traditionally focused on motor, syntactic and speech organization defects, but little is known about semantic processing integrity. We aimed to explore semantic processing in manifest HD by means of neurophysiological indexes and its association with other parameters derived from l...
Conference Paper
Background Frontal-related behavioral and cognitive symptoms, including perseveration, irritability and executive dysfunction, are characteristics of Huntington’s disease (HD). Although these symptoms can lead to maladaptive and reckless behaviors, few studies have delved into the prevalence, correlates and phenomenology of violent and criminal beh...
Conference Paper
Background Progression and age of onset are inversely linked to abnormal CAG repeat length in Huntington's disease (HD). However, the disparity in clinical outcomes among patients with equal repetitions suggests that additional variables affect HD. Tau protein, encoded by the microtubule-associated protein tau (MAPT) gene, exhibits an inversion pol...
Conference Paper
Background Recent evidence indicates that beyond the accumulation of mutant Huntingtin protein (mHTT), tau and other proteinopathies are associated with the clinical phenotypes of Huntington's disease (HD). Postmortem studies have suggested the presence of amyloid-beta and phosphorylated tau co-pathology in the HD brains,¹ but reports based on CSF...
Conference Paper
Thiamine (Vit B1) deficiencies (acquired or genetic) result in encephalopathies, some of which affect particularly the striatum, like that by mutations of the brain endothelium thiamine transporter (SLC19A3=ThTr2; OMIM #607483, Biotin and thiamine-responsive basal ganglia disease). Transcriptomic analyses of brain tissue from Huntington’s disease (...
Article
Background Emerging research implicates tau protein dysregulation in the pathophysiology of Huntington's disease. Objective This study investigated skin tau quantification as a potential biomarker for Huntington's disease and its correlation with disease burden outcomes. Methods In this cross‐sectional study, we measured skin tau levels using enz...
Article
Objective The effects of stimulation frequency on verbal fluency (VF) following subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD) are not well understood. The present study examines the impact stimulation frequency has on VF following bilateral STN-DBS in PD. Methods Prospective study of 38 consecutive patients with...
Article
Full-text available
Objective: Cognitive impairment in Parkinson's disease (PD) can show a very heterogeneous trajectory among patients. Here, we explored the mechanisms involved in the expression and prediction of different cognitive phenotypes over 4 years. Methods: In 2 independent cohorts (total n = 475), we performed a cluster analysis to identify trajectories o...
Preprint
Full-text available
We conducted the largest PSP GWAS of the Iberian population to date (522 cases from 22 Spanish and Portuguese institutions). We independently replicated seven known PSP risk variants, and unveiled a novel locus in NFASC/CNTN2 after meta-analysing our results with a newly available Dutch cohort and publicly available summary statistics. These findin...
Article
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Chorea is a hyperkinetic movement disorder associated with various underlyingconditions, including autoimmune diseases such as antiphospholipid syndrome (APS). APS can manifest with a wide range of neurological symptoms, including chorea. We present a case of a 77-year-old man with subacute generalized chorea secondary to primary APS. Notably, the...
Article
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Most neurodegenerative diseases lack definitive diagnostic tests, and the identification of easily accessible and reliable biomarkers remains a critical unmet need. Since tau protein is highly expressed in skin of tauopathies patients, we aimed to exploit the ultrasensitive seeding activity assay (SAA) to assess tau seeding activity in skin of pati...
Article
Background Levodopa‐induced dyskinesias (LID) are frequent in Parkinson's disease (PD). Objective To analyze the change in the frequency of LID over time, identify LID related factors, and characterize how LID impact on patients’ quality of life (QoL). Patients and Methods PD patients from the 5‐year follow‐up COPPADIS cohort were included. LID w...
Preprint
Full-text available
Background and objective Level of Education (LoE) is widely used as an indicator of cognitive reserve and is associated with risk of dementia. The aim of the present study was to know the influence of the LoE on the change in cognitive function (CF) in patients with Parkinson´s disease (PD). Patients and Methods Controls and PD patients from the S...
Article
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Background Apomorphine sublingual film (SL-APO) is an on-demand treatment for OFF episodes in patients with Parkinson’s disease (PD). Objective To assess the long-term (≥ 3 years) safety/tolerability and efficacy of SL-APO. Methods Study CTH-301 (http://www.clinicaltrials.gov NCT02542696; registered 2015-09-03) was a phase 3, multicentre, open-la...
Article
Full-text available
Objective The clinical phenotype of Huntington's disease (HD) can be very heterogeneous between patients, even when they share equivalent CAG repeat length, age, or disease burden. This heterogeneity is especially evident in terms of the cognitive profile and related brain changes. To shed light on the mechanisms participating in this heterogeneity...
Article
Full-text available
Parkinson’s disease (PD) is a neurodegenerative condition that is frequently associated with cognitive disorders. These can arise directly from the primary disease, or be triggered by external factors in susceptible individuals due to PD or other predisposing factors. The cognitive disorders encompass PD-associated cognitive impairment (PD-CI), del...
Article
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A key distinguishing factor between mild cognitive impairment (MCI) and dementia in Parkinson’s disease (PD) lies in the notable decrease in functioning due to cognitive impairment. The Parkinson’s Disease-Cognitive Functional Rating Scale (PD-CRFS) was developed to assess functional limitations caused by cognitive impairment, while reducing the in...
Article
Parkinson disease (PD) psychosis (PDP) is a spectrum of illusions, hallucinations and delusions that are associated with PD throughout its disease course. Psychotic phenomena can manifest from the earliest stages of PD and might follow a continuum from minor hallucinations to structured hallucinations and delusions. Initially, PDP was considered to...
Article
Full-text available
Hypomimia is a frequent manifestation in Parkinson's disease (PD) that can affect interpersonal relationships and quality of life. Recent studies have suggested that hypomimia is not only related to motor dysfunction but also to impairment in emotional processing networks. Therefore, we hypothesized that the severity of hypomimia could be associate...
Article
Background Frontal lobe signs in progressive supranuclear palsy (PSP) are prevalent and occur early in the disease. Although they are recognized in clinical practice, studies are needed to systematically investigate them for an in‐depth understanding of the neurological substrate and their potential prognostic implications in the disease. Objectiv...
Article
Full-text available
Ethnicity differences are an important determinant in the clinical manifestation of Parkinson’s disease (PD), but they are not yet widely recognized, particularly regarding the response to dopaminergic medications. The aim of this paper is to analyze the efficacy and safety of safinamide in Chinese patients with PD in the pivotal studies SETTLE and...
Preprint
Despite the advances in the understanding of Huntington's disease (HD), there is the need for molecular biomarkers to categorize mutation-carriers during the preclinical stage of the disease preceding the functional decline. Small RNAs (sRNAs) are a promising source of biomarkers since their expression levels are highly sensitive to pathobiological...
Article
Full-text available
Background and objective Recently, we demonstrated that staging Parkinson's disease (PD) with a novel simple classification called MNCD, based on four axes (motor, non‐motor, cognition, and dependency) and five stages, correlated with disease severity and patients’ quality of life. Here, we analyzed the correlation of MNCD staging with PD caregiver...
Chapter
TAR DNA-binding protein of 43 kDa (TDP-43) is a ubiquitously expressed ribonucleoprotein that participates in gene expression regulation. Since the discovery of aggregated TDP-43 as a pathological hallmark in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis (ALS) in 2006, this protein has been predominantly linked to neurodegener...
Article
Full-text available
A high burden of motor and non-motor parkinsonian symptoms is known to have a significant negative impact on the quality of life (QoL) of people with Parkinson’s disease (PD). Effective control of these symptoms with therapies that enable patients to maintain a good QoL is therefore a key treatment goal in PD management. When symptom control can no...
Article
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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...
Article
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Managing the many issues in advanced Parkinson’s disease (PD) requires education, continuous support, and specialized outpatient care involving a variety of allied healthcare professionals. It would be greatly appreciated if general neurologists and professionals from various disciplines who work with people diagnosed with Parkinson’s disease (PwP)...
Article
Background: Different types of therapies were proven effective for the medical management of motor and non-motor symptoms in Parkinson's disease (PD). We aimed to gain consensus on the Dopamine agonist (DA) therapy use in different clinical scenarios of Parkinson's disease (PD) patients. Methods: This consensus study was based on the nominal gro...
Article
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Background Recently, a novel simple classification called MNCD, based on 4 axes (Motor; Non-motor; Cognition; Dependency) and 5 stages, has been proposed to classify Parkinson's disease (PD). Objective Our aim was to apply the MNCD classification in a cohort of PD patients for the first time and also to analyze the correlation with quality of life...
Article
Despite decades of research, we do not definitively know how people sometimes see things that are not there. Eight models of complex visual hallucinations have been published since 2000, including Deafferentation, Reality Monitoring, Perception and Attention Deficit, Activation, Input, and Modulation, Hodological, Attentional Networks, Active infer...
Article
Background: Detection of suicidal ideation (SI) is key for trying to prevent suicide. The aim of this study was to analyze the frequency of SI and related factors in Spanish people with Parkinson's Disease (PwPD) and to compare them with a control group. Methods: PD patients and controls recruited from the Spanish cohort COPPADIS from January 20...
Article
Full-text available
Parkinson’s disease (PD) is a neurodegenerative disorder that leads to the degeneration of dopaminergic neurons resulting in a widespread pathology of motor and non-motor symptoms. Oral levodopa remains the most effective symptomatic treatment of PD, but motor complications such as Off episodes occur over time. The spectrum of manifestation of OFF...
Article
Full-text available
Introduction: Drooling in Parkinson's disease (PD) is frequent but often goes underrecognized. Our aim was to examine the prevalence of drooling in a PD cohort and compare it with a control group. Specifically, we identified factors associated with drooling and conducted subanalyses in a subgroup of very early PD patients. Patients and Methods. PD...
Article
Background: Cognitive impairment is a central feature of Huntington's disease (HD), but it is unclear to what extent more aggressive cognitive phenotypes exist in HD among individuals with the same genetic load and equivalence in other clinical and sociodemographic variables. Methods: We included Enroll-HD study participants in early and early-m...
Article
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Background: There is a need for identifying risk factors for hospitalization in Parkinson's disease (PD) and also interventions to reduce acute hospital admission. Objective: To analyze the frequency, causes, and predictors of acute hospitalization (AH) in PD patients from a Spanish cohort. Methods: PD patients recruited from 35 centers of Spain fr...
Article
Full-text available
Background and objective: Sex plays a role in Parkinson's disease (PD) mechanisms. We analyzed sex difference manifestations among Spanish patients with PD. Patients and methods: PD patients who were recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. A cross-sectional and a two-year follow-up analysis we...
Article
Full-text available
Individuals with pre‐manifest and early symptomatic Huntington's disease (HD) have shown deficits in solving arithmetic word‐problems. However, the neural correlates of these deficits in HD are poorly understood. We explored the structural (gray‐matter volume; GMV) and metabolic (18F‐FDG PET; SUVr) brain correlates of arithmetic performance using t...
Article
Full-text available
Background There is a need for identifying risk factors for hospitalization in Parkinson’s disease (PD) and also interventions to reduce acute hospital admission. Objective To analyze the frequency, causes, and predictors of acute hospitalization (AH) in PD patients from a Spanish cohort. Methods PD patients recruited from 35 centers of Spain fro...
Article
Background and purpose: Visual hallucinations (VH) and subjective cognitive complaints (SCC) are associated with cognitive impairment (CI) in Parkinson's disease. Our aims were to determine the association between VH and SCC and the risk of CI development in a cohort of patients with Parkinson's disease and normal cognition (PD-NC). Methods: Pat...
Article
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Aims The study's aim is to investigate the efficacy and safety of SOM3355 (bevantolol hydrochloride), a β1‐adrenoreceptor antagonist with recently identified vesicular monoamine transporter type 2 inhibitory properties, as a repositioned treatment to reduce chorea in Huntington's disease (HD). Methods A randomized, placebo‐controlled proof‐of‐conc...
Article
Background: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. Metho...
Preprint
Full-text available
Cognitive decline and hallucinations are common and debilitating non-motor symptoms, occurring during later phases of Parkinson's disease (PD). Minor hallucinations (MH), appear at early phases and have been suggested to predict cognitive impairment in PD, however, this has not been well-established by clinical research. Here, we investigated wheth...
Conference Paper
Background Although white matter (WM) abnormalities and subcortical iron accumulation are causal factors of neurodegeneration in Huntington’s disease (HD), their specific role is not clear yet. Aims: To understand the dynamics of the physiopathology process underlying in HD by using a multimodal temporo-spatial characterization of WM tracts (micros...
Conference Paper
Background Huntington’s disease (HD) is an inherited autosomal dominant disease characterized by progressive degeneration of the striatum and the cerebral cortex caused by a mutation in the Huntingtin gene comprising an expansion of a CAG repeat. Mutant huntingtin accumulates in endosomal compartments and triggers the activation of the endo-lysosom...
Conference Paper
Full-text available
Background Despite the advances in the understanding of Huntington’s disease (HD), no disease-modifying treatments exist, and therapeutic development and HD-clinical trials continue to fail. In this context, major efforts are focused on the assessment of measurable outcomes for optimal therapeutic response. Recent insights on HD described small non...
Article
A previously healthy woman began to present recurrent episodes of reduplicative paramnesia within her home and later structured visual hallucinations. The case was initially oriented as an incipient vascular dementia. Detailed anamnesis and neuropsychological examination suggested a rapidly progressive pattern of neuropsychological deficits mostly...
Article
Background Minor hallucinations in Parkinson's disease are associated with connectivity changes in attentional networks and increased risk of structured hallucinations. However, the clinical translation of these abnormalities in attention processes is not well-defined, and commonly used neuropsychological tests are not able to detect significant de...
Article
Full-text available
Objectives: To evaluate if the feedback related negativity (FRN) -a neurophysiological marker of incentive processing- can be used to predict the development of impulse control disorders (ICD) in Parkinson's disease (PD) METHODS: Longitudinal cohort of consecutive non-demented Parkinson's disease patients with no ICD history. We recorded FRN signa...
Article
Full-text available
Background Patients with Huntington’s disease (HD) exhibit a variable predominance of cognitive, behavioral and motor symptoms. A specific instrument focusing on the impact of cognitive impairment in HD over functional capacity is lacking. Objective To address the need for a brief and specifically developed HD questionnaire able to capture functio...
Article
Full-text available
Background and purpose: Reduced facial expression of emotions is a very frequent symptom of Parkinson's disease (PD) and has been considered part of the motor features of the disease. However, the neural correlates of hypomimia and the relationship between hypomimia and other non-motor symptoms of PD are poorly understood. Methods: The clinical...
Article
Background: Cognitive dysfunction is a disabling complication in Parkinson's disease (PD). Accuracy of diagnosis of mild cognitive impairment in PD (PD-MCI) depends on the tests performed, which limits results generalization. Blood-based biomarkers could provide additional objective information for PD-MCI diagnosis and progression. Blood neurofila...