RESUMEN
Around 80% of persons with Parkinson's disease (PD) present symptoms of dysphagia. Although cognitive impairment may contribute to dysphagia, few studies have investigated the association between the PD neuropsychological profile and objective measures of swallowing dysfunction. Since the swallowing function comprises involuntary but also voluntary actions, we hypothesize that specific measures of attention and executive functions can be underlined in PD-related dysphagia. Therefore, the aim of this study was to extensively investigate the correlation and the relationship between attentive and executive functions and safety/efficiency of pharyngeal phase of swallowing in people with PD. All participants received a fiberoptic endoscopic evaluation of swallowing and were evaluated using the Penetration Aspiration Scale (PAS); the Yale Pharyngeal Residue Severity Rating Scale (IT-YPRSRS), and the Functional Oral Intake Scale (FOIS-IT). Participants also underwent a neuropsychological assessment covering global cognitive status, attention, and frontal executive functions. Correlations and associations between neuropsychological measures and swallowing components were calculated. Twenty-one participants with PD (mean age 69.38 ± 6.58 years, mean disease duration 8.38 ± 5.31 years; mean MDS-UPDRS III 43.95 ± 24.18) completed all evaluations. The most significant correlations were found between attentive functions (i.e., Stroop Time), and executive functions (i.e., Raven's Progressive Matrices, Digit Backward and Semantic Fluency), and FOIS-IT, PAS, and IT-YPRSRS sinuses and valleculae. These associations were not influenced by disease duration. These results suggest that a dysfunction to attentional processes and/or to executive functions can contribute to penetration and the presence of pharyngeal residue in participants with middle-stage PD.
RESUMEN
While extensive research has documented the cognitive changes associated with Parkinson's disease (PD), a relatively small portion of the empirical literature investigated the language abilities of individuals with PD. Recently, artificial intelligence applied to linguistic data has shown promising results in predicting the clinical diagnosis of neurodegenerative disorders, but a deeper investigation of the current literature available on PD is lacking. This systematic review investigates the nature of language disorders in PD by assessing the contribution of machine learning (ML) to the classification of patients with PD. A total of 10 studies published between 2016 and 2023 were included in this review. Tasks used to elicit language were mainly structured or unstructured narrative discourse. Transcriptions were mostly analyzed using Natural Language Processing (NLP) techniques. The classification accuracy (%) ranged from 43 to 94, sensitivity (%) ranged from 8 to 95, specificity (%) ranged from 3 to 100, AUC (%) ranged from 32 to 97. The most frequent optimal linguistic measures were lexico-semantic (40%), followed by NLP-extracted features (26%) and morphological consistency features (20%). Artificial intelligence applied to linguistic markers provides valuable insights into PD. However, analyzing measures derived from narrative discourse can be time-consuming, and utilizing ML requires specialized expertise. Moving forward, it is important to focus on facilitating the integration of both narrative discourse analysis and artificial intelligence into clinical practice.
RESUMEN
BACKGROUND: The number of deep brain stimulation (DBS) procedures is rapidly rising as well as the novel indications. Reporting adverse events related to surgery and to the hardware used is essential to define the risk-to-benefit ratio and develop novel strategies to improve it. OBJECTIVE: To analyze DBS complications (both procedure-related and hardware-related) and further assess potential predictive factors. METHODS: Five hundred seventeen cases of DBS for Parkinson's disease were performed between 2006 and 2021 in a single center (mean follow-up: 4.68 ± 2.86 years). Spearman's Rho coefficient was calculated to search for a correlation between the occurrence of intracerebral hemorrhage (ICH) and the number of recording tracks. Multiple logistic regression analyzed the probability of developing seizures and ICH given potential risk factors. Kaplan-Meier curves were performed to analyze the cumulative proportions of hardware-related complications. RESULTS: Mortality rate was 0.2%, while permanent morbidity 0.6%. 2.5% of cases suffered from ICH which were not influenced by the number of tracks used for recordings. 3.3% reported seizures that were significantly affected by perielectrode brain edema and age. The rate of perielectrode brain edema was significantly higher for Medtronic's leads compared to Boston Scientific's (Χ2(1)= 5.927, P= 0.015). 12.2% of implants reported Hardware-related complications, the most common of which were wound revisions (7.2%). Internal pulse generator models with smaller profiles displayed more favorable hardware-related complication survival curves compared to larger designs (X2(1)= 8.139, P= 0.004). CONCLUSION: Overall DBS has to be considered a safe procedure, but future research is needed to decrease the rate of hardware-related complications which may be related to both the surgical technique and to the specific hardware's design. The increased incidence of perielectrode brain edema associated with certain lead models may likewise deserve future investigation.
Asunto(s)
Edema Encefálico , Estimulación Encefálica Profunda , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/terapia , Estimulación Encefálica Profunda/efectos adversos , Estimulación Encefálica Profunda/métodos , Edema Encefálico/etiología , Hemorragia Cerebral/epidemiología , Hemorragia Cerebral/etiología , Convulsiones/etiología , Electrodos Implantados/efectos adversos , Estudios RetrospectivosRESUMEN
Growing evidence suggests that inflammation contributes to brain aging and neurodegeneration. This study investigates the relationship between global cognitive as well executive function and the inflammatory markers IL-6, CRP, and TNF-α in a population-based study of older adults. A population-based sample, of older people in Southern Italy, was enrolled. We measured serum levels of IL-6, CRP, and TNF-α. We also administered two neuropsychological tests: Mini-Mental State Examination and Frontal Assessment Battery. Rank-based regression models were performed to investigate the relationship between inflammatory markers and cognitive functions, including major demographic and clinical confounders for adjustment. The sample consisted of 1929 subjects aged between 65 and 95 years. Multivariate linear regression analysis revealed that higher serum levels of IL-6 were associated with lower MMSE and FAB scores even after adjustment for demographic data and cardiovascular risk factors. No significant associations were found between cognitive functioning and serum levels of CRP and TNF-α. Our results suggest that higher levels of IL-6 were associated with cognitive impairment in an older adult population of Southern Italy.
RESUMEN
BACKGROUND AND OBJECTIVES: In Italy, approximately 650 individuals receive a diagnosis of primary progressive aphasia (PPA) every year. Unfortunately, the frequency with which patients are referred to speech-language services is suboptimal, likely due to skepticism regarding the value of speech-language therapy in the context of neurodegeneration. MATERIALS AND METHODS: We conducted a virtual survey of speech and language therapists (SLTs) across Italy, to collect information about the assessment, intervention and management of patients with PPA. To ensure that as many SLTs as possible received the survey, the Italian Federation of SLTs (Federazione Logopedisti Italiani, FLI) aided in disseminating the survey. RESULTS: In total, 336 respondents participated in the online survey, 140 of whom had previous experience with PPA patients. Respondents indicated having seen a total of 428 PPA patients in the previous 24 months (three patients on average, range: 0-40). SLTs who reported never working with PPA identified underdiagnoses, low referral rates and the rarity of the clinical syndrome as major reasons for their lack of experience with PPA. SLTs with experience working with PPA indicated that patients may not have accessed services because of service dysfunction and geographical barriers. Respondents reported using informal interviews during assessments and tests developed for post-stroke aphasia, while impairment-based/restitutive interventions were utilised most often. CONCLUSION: Findings may serve to inform health policy organisations regarding the current shortcomings and needed recommendations for improving the care of individuals with PPA in Italy. Improving awareness of the utility of rehabilitation among SLTs and other clinical service providers may serve to facilitate access to intervention, which in turn will serve to better support individuals living with PPA. WHAT THIS PAPER ADDS: What is already known on the subject Speech and language therapists (SLTs) play a crucial role in the assessment, diagnosis and treatment of people with primary progressive aphasia (PPA). However, the frequency with which individuals with PPA are referred for speech and language services is suboptimal due to skepticism regarding the value of speech and language therapy in the context of neurodegeneration, the scarcity of SLTs with expertise in the treatment of PPA and the lack of awareness of the SLT role amongst referrers. What this paper adds to existing knowledge In recognition of the lack of published information on the provision of speech and language therapy services and clinicians' approaches to the assessment and treatment of individuals with PPA in Italy, we conducted an online survey to evaluate the current referral patterns for speech and language therapy services and to examine the current barriers to access these services for individuals with PPA in Italy. What are the potential or actual clinical implications of this work? The data presented here support that SLTs view treatment as useful for individuals with PPA and other professional figures and may serve to improve access to intervention, which in turn will serve to better support individuals living with PPA. The results highlight the need to inform health policy organisations about current gaps and aid in developing recommendations for improving the care of individuals with PPA, in order to understand how SLTs can best support individuals with PPA and their families.
Asunto(s)
Afasia Progresiva Primaria , Terapia del Lenguaje , Logopedia , Humanos , Afasia Progresiva Primaria/diagnóstico , Afasia Progresiva Primaria/terapia , Terapia del Lenguaje/métodos , Derivación y Consulta , Habla , Logopedia/métodos , Encuestas y Cuestionarios , Accesibilidad a los Servicios de Salud , ItaliaRESUMEN
OBJECTIVES: There is a lack of effective biomarkers for neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia. Extracellular vesicle (EV) RNA cargo can have an interesting potential as a non-invasive biomarker for NDs. However, the knowledge about the abundance of EV-mRNAs and their contribution to neurodegeneration is not clear. METHODS: Large and small EVs (LEVs and SEVs) were isolated from plasma of patients and healthy volunteers (control, CTR) by differential centrifugation and filtration, and RNA was extracted. Whole transcriptome was carried out using next generation sequencing (NGS). RESULTS: Coding RNA (i.e., mRNA) but not long non-coding RNAs (lncRNAs) in SEVs and LEVs of patients with ALS could be distinguished from healthy CTRs and from other NDs using the principal component analysis (PCA). Some mRNAs were found in commonly deregulated between SEVs of patients with ALS and frontotemporal dementia (FTD), and they were classified in mRNA processing and splicing pathways. In LEVs, instead, one mRNA and one antisense RNA (i.e., MAP3K7CL and AP003068.3) were found to be in common among ALS, FTD, and PD. No deregulated mRNAs were found in EVs of patients with AD. CONCLUSION: Different RNA regulation occurs in LEVs and SEVs of NDs. mRNAs and lncRNAs are present in plasma-derived EVs of NDs, and there are common and specific transcripts that characterize LEVs and SEVs from the NDs considered in this study.
RESUMEN
The etiology of Parkinson's disease (PD) is presumably multifactorial and likely involves interactions between genetic and environmental factors, as well as mitochondrial dysfunction, oxidative stress and inflammation. Among environmental factors, Vitamin D was reported to associate with the risk of PD. Vitamin D activity is mediated by its binding to the vitamin D Receptor (VDR), a transcriptional factor for almost 3% of human genes. We genotyped for ApaI, BsmI, TaqI, FokI and rs1989969 VDR single nucleotide polymorphisms (SNPs) a cohort of 406 PD and 800 healthy controls (HC) and found a strong association between the FokI (rs2228570) VDR SNP and PD. Thus, the TT genotype and the T allele resulted associated with PD in the overall analyzed PD population. Gender-based stratification of data indicated that results were maintained for FokI TT genotype and T allele in male PD patients, whereas the FokI T allele alone was confirmed as a risk factor for PD in females. Co-segregation analyses indicated the TaqI ApaI FokI rs1989969 GCTG as a "risk" haplotype for PD. In a subgroup of patients and controls neural Vitamin D and VDR concentration was analyzed in extravesicles (NDEVs) isolated from peripheral blood: no differences emerged between PD and HC. NDEVs results will need to be validated in ampler cohort but we can speculate that, if at neuronal level the amounts of Vitamin D and of VDR are comparable, than the bioavailability of vitamin D and the efficacy of the vitamin D/VDR axis is differentially modulated in PD by VDR SNPs.
Asunto(s)
Enfermedad de Parkinson , Receptores de Calcitriol , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Masculino , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple , Receptores de Calcitriol/genéticaRESUMEN
BACKGROUND: Adult-onset focal dystonia can spread to involve one, or less frequently, two additional body regions. Spread of focal dystonia to a third body site is not fully characterized. MATERIALS AND METHODS: We retrospectively analyzed data from the Italian Dystonia Registry, enrolling patients with segmental/multifocal dystonia involving at least two parts of the body or more. Survival analysis estimated the relationship between dystonia features and spread to a third body part. RESULTS: We identified 340 patients with segmental/multifocal dystonia involving at least two body parts. Spread of dystonia to a third body site occurred in 42/241 patients (17.4%) with focal onset and 10/99 patients (10.1%) with segmental/multifocal dystonia at onset. The former had a greater tendency to spread than patients with segmental/multifocal dystonia at onset. Gender, years of schooling, comorbidity, family history of dystonia/tremor, age at dystonia onset, and disease duration could not predict spread to a third body site. Among patients with focal onset in different body parts (cranial, cervical, and upper limb regions), there was no association between site of focal dystonia onset and risk of spread to a third body site. DISCUSSION AND CONCLUSION: Spread to a third body site occurs in a relative low percentage of patients with idiopathic adult-onset dystonia affecting two body parts. Regardless of the site of dystonia onset and of other demographic/clinical variables, focal onset seems to confer a greater risk of spread to a third body site in comparison to patients with segmental/multifocal dystonia at onset.
Asunto(s)
Trastornos Distónicos/epidemiología , Trastornos Distónicos/fisiopatología , Sistema de Registros , Extremidad Superior/fisiopatología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Cuello/fisiopatología , Estudios Retrospectivos , Cráneo/fisiopatología , Tortícolis/epidemiología , Tortícolis/fisiopatologíaRESUMEN
Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder caused by the deposition of amyloid beta-peptide (Aß) aggregates. Aß aggregates lead to vessel rupture and intracerebral hemorrhages, detected by magnetic resonance imaging (MRI). Presenile CAA is usually genetically determined by mutations in the amyloid precursor protein (APP) gene. However, mutations after codon 200 in the presenilin 1 (PSEN1) gene have been reported to facilitate CAA onset. Here, we analyzed the genetic bases in a patient of 55 years old affected by CAA and cognitive decline. DNA was isolated and genetic analysis was performed by Next-Generation Sequencing (NGS). RNA was extracted and retro-transcribed to perform segregation analysis by TOPO-TA cloning. WB analysis was carried out to check the impact of the mutations on protein. Two compound heterozygous mutations in PSEN1 exon 10, such as a novel stop-gain mutation (c.1070C > G) and a pathogenic splice variant (c.1129A > T), were found by NGS. Both mutations altered the presenilin 1 protein, truncating its C-terminal portion. This is the first case of CAA and cognitive decline caused by two compound mutations in PSEN1. With this report, we suggest extending the genetic analysis to PSEN1 when cerebral microbleeds are observed by MRI investigation in a patient affected by presenile cognitive decline.
Asunto(s)
Angiopatía Amiloide Cerebral/diagnóstico , Angiopatía Amiloide Cerebral/genética , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/genética , Mutación , Presenilina-1/genética , Alelos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Análisis Mutacional de ADN , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Modelos Moleculares , Fenotipo , Presenilina-1/química , Conformación ProteicaRESUMEN
OBJECTIVE: To determine changes in clinical features and striatal dopamine reuptake transporter (DAT) density after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: Participants with probable iNPH were assessed at baseline by means of clinical rating scales, brain MRI, and SPECT with [123I]-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane (FP-CIT). Levodopa responsiveness was also evaluated. Patients who did or did not undergo lumboperitoneal shunt were clinically followed up and repeated SPECT after 2 years. RESULTS: We enrolled 115 patients with iNPH. Of 102 patients without significant levodopa response and no signs of atypical parkinsonism, 92 underwent FP-CIT SPECT (58 also at follow-up) and 59 underwent surgery. We identified a disequilibrium subtype (phenotype 1) and a locomotor subtype (phenotype 2) of higher-level gait disorder. Gait impairment correlated with caudate DAT density in both phenotypes, whereas parkinsonian signs correlated with putamen and caudate DAT binding in patients with phenotype 2, who showed more severe symptoms and lower striatal DAT density. Gait and caudate DAT binding improved in both phenotypes after surgery (p < 0.01). Parkinsonism and putamen DAT density improved in shunted patients with phenotype 2 (p < 0.001). Conversely, gait, parkinsonian signs, and striatal DAT binding worsened in patients who declined surgery (p < 0.01). CONCLUSIONS: This prospective interventional study highlights the pathophysiologic relevance of striatal dopaminergic dysfunction in the motor phenotypic expression of iNPH. Absence of levodopa responsiveness, shunt-responsive parkinsonism, and postsurgery improvement of striatal DAT density are findings that corroborate the notion of a reversible striatal dysfunction in a subset of patients with iNPH.
Asunto(s)
Derivaciones del Líquido Cefalorraquídeo , Dopaminérgicos/administración & dosificación , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Trastornos Neurológicos de la Marcha , Hidrocéfalo Normotenso , Neostriado , Evaluación de Resultado en la Atención de Salud , Trastornos Parkinsonianos , Equilibrio Postural , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/fisiopatología , Humanos , Hidrocéfalo Normotenso/complicaciones , Hidrocéfalo Normotenso/metabolismo , Hidrocéfalo Normotenso/cirugía , Levodopa/administración & dosificación , Masculino , Neostriado/diagnóstico por imagen , Neostriado/metabolismo , Neostriado/fisiopatología , Trastornos Parkinsonianos/tratamiento farmacológico , Trastornos Parkinsonianos/etiología , Trastornos Parkinsonianos/fisiopatología , Fenotipo , Equilibrio Postural/efectos de los fármacos , Equilibrio Postural/fisiología , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Identifying biomarkers is essential for early diagnosis of neurodegenerative diseases (NDs). Large (LEVs) and small extracellular vesicles (SEVs) are extracellular vesicles (EVs) of different sizes and biological functions transported in blood and they may be valid biomarkers for NDs. The aim of our study was to investigate common and different miRNA signatures in plasma derived LEVs and SEVs of Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Dementia (FTD) patients. LEVs and SEVs were isolated from plasma of patients and healthy volunteers (CTR) by filtration and differential centrifugation and RNA was extracted. Small RNAs libraries were carried out by Next Generation Sequencing (NGS). MiRNAs discriminate all NDs diseases from CTRs and they can provide a signature for each NDs. Common enriched pathways for SEVs were instead linked to ubiquitin mediated proteolysis and Toll-like receptor signaling pathways and for LEVs to neurotrophin signaling and Glycosphingolipid biosynthesis pathway. LEVs and SEVs are involved in different pathways and this might give a specificity to their role in the spreading of the disease. The study of common and different miRNAs transported by LEVs and SEVs can be of great interest for biomarker discovery and for pathogenesis studies in neurodegeneration.
Asunto(s)
MicroARN Circulante/sangre , Vesículas Extracelulares/metabolismo , Perfilación de la Expresión Génica , Enfermedades Neurodegenerativas/sangre , Transducción de Señal , Anciano , Anciano de 80 o más Años , MicroARN Circulante/genética , Vesículas Extracelulares/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Neurodegenerativas/genéticaRESUMEN
BACKGROUND: Idiopathic normal pressure hydrocephalus can present with parkinsonism. However, abnormalities of the striatal dopamine reuptake transporter are unclear. OBJECTIVES: To explore presence and features of striatal dopaminergic deficit in subjects with idiopathic normal pressure hydrocephalus as compared to Parkinson's disease (PD) patients and healthy controls. METHODS: We investigated 50 subjects with idiopathic normal pressure hydrocephalus, 25 with PD, and 40 healthy controls. All participants underwent [123 I]-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane and single-photon emission computed tomography to quantify the striatal dopamine reuptake transporter binding. All subjects with idiopathic normal pressure hydrocephalus underwent a levodopa (l-dopa) challenge test and magnetic resonance imaging to evaluate ventriculomegaly and white matter changes. Gait, cognition, balance, and continence were assessed with the Idiopathic Normal Pressure Hydrocephalus Rating Scale, and parkinsonism with the motor section of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale. All patients completed a 2-year follow-up. RESULTS: A total of 62% of patients with idiopathic normal pressure hydrocephalus featured a reduced striatal dopamine reuptake transporter binding, which correlated with the severity of parkinsonism but not with features of ventriculomegaly or white matter changes. Unlike PD, this dopaminergic deficit in idiopathic normal pressure hydrocephalus was more symmetric and prominent in the caudate nucleus. CONCLUSIONS: Subjects with idiopathic normal pressure hydrocephalus can present a reduction of striatal dopamine reuptake transporter binding, which is consistent with the severity of parkinsonism and qualitatively differs from that found in PD patients. Longitudinal interventional studies are needed to prove a role for striatal dopamine reuptake transporter deficit in the pathophysiology of idiopathic normal pressure hydrocephalus. © 2020 International Parkinson and Movement Disorder Society.
Asunto(s)
Hidrocéfalo Normotenso , Trastornos Motores , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/metabolismo , Dopamina , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Humanos , Hidrocéfalo Normotenso/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , TropanosRESUMEN
Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders characterized by a progressive degeneration of the central or peripheral nervous systems. A central role of the RNA metabolism has emerged in these diseases, concerning mRNAs processing and non-coding RNAs biogenesis. We aimed to identify possible common grounds or differences in the dysregulated pathways of AD, PD, and ALS. To do so, we performed RNA-seq analysis to investigate the deregulation of both coding and long non-coding RNAs (lncRNAs) in ALS, AD, and PD patients and controls (CTRL) in peripheral blood mononuclear cells (PBMCs). A total of 293 differentially expressed (DE) lncRNAs and 87 mRNAs were found in ALS patients. In AD patients a total of 23 DE genes emerged, 19 protein coding genes and four lncRNAs. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses, we found common affected pathways and biological processes in ALS and AD. In PD patients only five genes were found to be DE. Our data brought to light the importance of lncRNAs and mRNAs regulation in three principal neurodegenerative disorders, offering starting points for new investigations on deregulated pathogenic mechanisms.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Esclerosis Amiotrófica Lateral/metabolismo , Enfermedad de Parkinson/metabolismo , Enfermedad de Alzheimer/genética , Esclerosis Amiotrófica Lateral/genética , Humanos , Enfermedad de Parkinson/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Mensajero/metabolismo , RNA-SeqRESUMEN
BACKGROUND: Sleep disorders and cognitive impairment are frequently reported in Parkinson's disease (PD) as non-motor disabling symptoms. While it is known that REM sleep Behaviour Disorder (RBD) in PD is associated with motor and cognitive decline, little is known about the neurobiological significance of NREM sleep arousal-related disorders. OBJECTIVES: to evaluate the cognitive and clinical correlates of arousal-related disorders in PD. METHODS: Clinical data and video-polysomnography were analysed from one hundred-seventy consecutive subjects with PD. Based on the neuropsychological assessment, the subjects were divided into three groups: no cognitive impairment (PD; n = 58), mild cognitive impairment (PD-MCI; n = 58) and overt dementia (PDD; n = 54). RESULTS: Arousal-related disorders by history were reported in 32.9% of the subjects: 10.3% PD, 31.6% PD-MCI and 59.3% PDD (p = 0.001). Video-PSG captured arousal-related disorders in 1.7% PD, 21.2% MCI-PD and 35.6% PDD (p = 0.001). Arousal-related disorders and RBD were recorded in the same night in 7.7% PD, 9.8% MCI-PD and 15.6% PDD (p = 0.04). Patients with arousal-related disorders captured at V-PSG have a longer disease duration (p = 0.003), higher UPDRS score (p = 0.039), longer duration of treatment with levodopa (p = 0.017) and dopamine agonists (p = 0.018), worse H&Y staging (p = 0.001), lower MMSE score (p = 0.019) and more frequently hallucinations (p = 0.004). In multivariate analysis, cognitive impairment significantly increases the risk of arousal-related disorders (OR 3.387-95% CI 1.395-8.220, p = 0.007). CONCLUSION: Arousal-related disorders appear to be a marker of cognitive decline in PD. Recognizing arousal-related disorders should make clinicians aware of a possible cognitive decline in PD and eventually modify the therapeutic approach.
Asunto(s)
Disfunción Cognitiva , Enfermedad de Parkinson , Trastorno de la Conducta del Sueño REM , Nivel de Alerta , Disfunción Cognitiva/etiología , Humanos , Enfermedad de Parkinson/complicaciones , SueñoRESUMEN
Introduction: Cervical dystonia (CD) is one of the most common forms of adult-onset isolated dystonia. Recently, CD has been classified according to the site of onset and spread, in different clinical subgroups, that may represent different clinical entities or pathophysiologic subtypes. In order to support this hypothesis, in this study we have evaluated whether different subgroups of CD, that clinically differ for site of onset and spread, also imply different sensorimotor features. Methods: Clinical and demographic data from 842 patients with CD from the Italian Dystonia Registry were examined. Motor features (head tremor and tremor elsewhere) and sensory features (sensory trick and neck pain) were investigated. We analyzed possible associations between motor and sensory features in CD subgroups [focal neck onset, no spread (FNO-NS); focal neck onset, segmental spread (FNO-SS); focal onset elsewhere with segmental spread to neck (FOE-SS); segmental neck involvement without spread (SNI)]. Results: In FNO-NS, FOE-SS, and SNI subgroups, head tremor was associated with the presence of tremor elsewhere. Sensory trick was associated with pain in patients with FNO-NS and with head tremor in patients with FNO-SS. Conclusion: The frequent association between head tremor and tremor elsewhere may suggest a common pathophysiological mechanism. Two mechanisms may be hypothesized for sensory trick: a gating mechanism attempting to reduce pain and a sensorimotor mechanism attempting to control tremor.
RESUMEN
Idiopathic normal pressure hydrocephalus (iNPH) is a common neurological disorder with unknown etiology. A selective depletion of aquaporin 4 (AQP4) has been shown in iNPH patients. We collected serum and cerebrospinal fluid (CSF) from 43 iNPH patients and 35 with other neurodegenerative conditions, and serum from 43 healthy subjects. All samples were tested for AQP4-IgG/IgA/IgM antibodies using a live cell-based assay. No patients or controls had serum/CSF AQP4-IgG/IgA. One/43 iNPH patient and 0/43 controls tested positive for serum AQP4-IgM. The AQP4-IgM-positive iNPH patient had no clinico-radiological distinctive features. AQP4 antibodies are unlikely to play a role in iNPH pathogenesis.
Asunto(s)
Acuaporina 4/sangre , Acuaporina 4/líquido cefalorraquídeo , Autoanticuerpos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Hidrocéfalo Normotenso/sangre , Hidrocéfalo Normotenso/líquido cefalorraquídeo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Femenino , Humanos , Hidrocéfalo Normotenso/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Cervical dystonia is associated with neck pain in a significant proportion of cases, but the mechanisms underlying pain are largely unknown. In this exploratory study, we compared demographic and clinical variables in cervical dystonia patients with and without neck pain from the Italian Dystonia Registry. Univariable and multivariable logistic regression analysis indicated a higher frequency of sensory trick and a lower educational level among patients with pain.
Asunto(s)
Trastornos Distónicos , Tortícolis , Demografía , Humanos , Dolor de Cuello/epidemiología , Tortícolis/complicaciones , Tortícolis/epidemiologíaRESUMEN
BACKGROUND: Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD). The impact of different variants on the PD clinical spectrum is still unclear. OBJECTIVES: We determined the frequency of GBA-related PD in Italy and correlated GBA variants with motor and nonmotor features and their occurrence over time. METHODS: Sanger sequencing of the whole GBA gene was performed. Variants were classified as mild, severe, complex, and risk. ß-glucocerebrosidase activity was measured. The Kaplan-Meier method and Cox proportional hazard regression models were performed. RESULTS: Among 874 patients with PD, 36 variants were detected in 14.3%, including 20.4% early onset. Patients with GBA-PD had earlier and more frequent occurrence of several nonmotor symptoms. Patients with severe and complex GBA-PD had the highest burden of symptoms and a higher risk of hallucinations and cognitive impairment. Complex GBA-PD had the lowest ß-glucocerebrosidase activity. CONCLUSIONS: GBA-PD is highly prevalent in Italy. Different types of mutations underlie distinct phenotypic profiles. © 2020 International Parkinson and Movement Disorder Society.