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Processing of quantifiers such as "many" and "few" relies on number knowledge, linguistic abilities, and working memory. Negative quantifiers (e.g., "few," "less than half") induce higher processing costs than their positive counterparts. Furthermore, the meaning of some quantifiers is flexible and thus adaptable. Importantly, in neurotypical individuals, changing the meaning of one quantifier also leads to a generalized change in meaning for its polar opposite (e.g., the change of the meaning of "many" leads to the change of that of "few"). Here, we extended this research to patients with fluent and non-fluent aphasia after stroke. In two experiments, participants heard sentences of the type "Many/few of the circles are yellow/blue," each followed by a picture with different quantities of blue and yellow circles. The participants judged whether the sentence adequately described the picture. Each experiment consisted of three blocks: a baseline block to assess the participants' criteria for both quantifiers, a training block to shift the criteria for "many," and a test block, identical to the baseline to capture any changes in quantifier semantics. In Experiment 1, the change of the meaning of "many" was induced by using adaptation to small numbers (20-50%) of circles of the named color. In Experiment 2, explicit feedback was given in the training block after each response to rate proportions of 40% (or higher) as "many," whereas 40% is normally rather rated as "few." The objective was to determine whether people with fluent or non-fluent aphasia were able to process quantifiers appropriately and whether generalized semantic flexibility was present after brain damage. Sixteen out of 21 patients were able to perform the task. People with fluent aphasia showed the expected polarity effect in the reaction times and shifted their criteria for "many" with generalization to the untrained quantifier "few." This effect, however, was only obtained after explicit feedback (Experiment 2) but not by mere adaptation (Experiment 1). In contrast, people with non-fluent aphasia did not change the quantifier semantics in either experiment. This study contributes to gaining new insights into quantifier processing and semantic flexibility in people with aphasia and general underlying processing mechanisms.
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INTRODUCTION: Frailty is a syndrome depicting vulnerability of multiple physiological systems to stressors. Frailty measures, such as Hospital Frailty Risk Score (HFRS), can be used to identify frailty and predict outcome more reliably. Our aim was to analyse a blood-based frailty index (FI-B) at admission for prediction outcome of patients with acute ischemic stroke (AIS) undergoing endovascular treatment (EVT). METHODS: We conducted a retrospective study of consecutive AIS patients undergoing EVT in a single tertiary centre during a period of five years. A set of eighteen blood parameters at admission were collected and nine of these were utilized to calculate FI-B. We analysed the relationship between FI-B and HFRS. We examined the baseline characteristics of the study population based on FI-B-tertiles. Multivariable regression models were employed to ascertain the association between FI-B and in-hospital mortality, 3-month mortality and 3-month functional outcome. RESULTS: The final study population comprised 489 patients, with a median age of 75.6 years, 49.5% of patients were male. The FI-B exhibited a weak positive correlation with HFRS (rho=0.113, p=0.016). Patients in higher FI-B-tertiles were older and more frequently presented with pre-stroke functional dependence and comorbidities. Moreover, an increasing FI-B was independently associated with increased likelihood of in-hospital mortality (adjusted odds ratio [aOR]=1.29, 95% confidence interval [95%CI]=1.14-1.47), 3-month mortality (aOR=1.26, 95%CI=1.11-1.43), and of increasing 3-month functional disability measured by utility-weighted modified Rankin Scale (common aOR=0.84, 95%CI=0.76-0.93). CONCLUSION: A frailty index based on blood values at admission was able to identify frailty in AIS patients undergoing EVT and was an independent predictor of short- and medium-term outcome after stroke.
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BACKGROUND: Neurogenic dysphagia is a frequent complication of stroke and is associated with aspiration pneumonia and poor outcomes. Although ischaemic lesion location and size are major determinants of the presence and severity of post-stroke dysphagia, little is known about the contribution of other acute stroke-unrelated factors. We aimed to analyse the impact of swallowing and non-swallowing muscles measurements on swallowing function after large vessel occlusion stroke. METHODS: This retrospective study was based on a prospective registry of consecutive ischaemic stroke patients. Patients who underwent mechanical thrombectomy between July 2021 and June 2022 and received a flexible endoscopic evaluation of swallowing (FEES) within 5 days after admission were included. Demographic, anthropometric, clinical, and imaging data were collected from the registry. The cross-sectional areas (CSA) of selected swallowing muscles (as a surrogate marker for swallowing muscle mass) and of cervical non-swallowing muscles were measured in computed tomography. Skeletal muscle index (SMI) was calculated and used as a surrogate marker for whole body muscle mass. FEES parameters, namely, Functional Oral Intake Scale (FOIS, as a surrogate marker for dysphagia presence and severity), penetration aspiration scale, and the presence of moderate-to-severe pharyngeal residues were collected from the clinical records. Univariate and multivariate ordinal and logistic regression analyses were performed to analyse if total CSA of swallowing muscles and SMI were associated with FEES parameters. RESULTS: The final study population consisted of 137 patients, 59 were female (43.1%), median age was 74 years (interquartile range 62-83), median baseline National Institutes of Health Stroke Scale score was 12 (interquartile range 7-16), 16 patients had a vertebrobasilar occlusion (11.7%), and successful recanalization was achieved in 127 patients (92.7%). Both total CSA of swallowing muscles and SMI were significantly correlated with age (rho = -0.391, P < 0.001 and rho = -0.525, P < 0.001, respectively). Total CSA of the swallowing muscles was independently associated with FOIS (common adjusted odds ratio = 1.08, 95% confidence interval = 1.01-1.16, P = 0.029), and with the presence of moderate-to-severe pharyngeal residues for puree consistencies (adjusted odds ratio = 0.90, 95% confidence interval = 0.81-0.99, P = 0.036). We found no independent association of SMI with any of the FEES parameters. CONCLUSIONS: Baseline swallowing muscle mass contributes to the pathophysiology of post-stroke dysphagia. Decreasing swallowing muscle mass is independently associated with increasing severity of early post-stroke dysphagia and with increased likelihood of moderate-to-severe pharyngeal residues.
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Trastornos de Deglución , Deglución , Accidente Cerebrovascular Isquémico , Trombectomía , Humanos , Trastornos de Deglución/etiología , Masculino , Femenino , Anciano , Accidente Cerebrovascular Isquémico/complicaciones , Trombectomía/métodos , Deglución/fisiología , Persona de Mediana Edad , Estudios Retrospectivos , Anciano de 80 o más Años , Músculo Esquelético/fisiopatologíaRESUMEN
BACKGROUND: Aphasia is a devastating consequence after stroke, affecting millions of patients each year. Studies have shown that intensive speech and language therapy (SLT) is effective in the chronic phase of aphasia. Leveraging a large single-center cohort of persons with aphasia (PWA) including patients also in the subacute phase, we assessed treatment effects of intensive aphasia therapy in a real-world setting. METHODS: Data were collected at the Aachen aphasia ward in Germany between 2003 and 2020. Immediate treatment responses across different language domains were assessed with the Aachen Aphasia Test (AAT) using single-case psychometrics, conducted before and after 6-7 weeks of intensive SLT (10 h per week, median (IQR) dosage = 68 (61-76)). We adjusted for spontaneous recovery in subacute patients. Differential treatment effects between subgroups of chronicity and predictors of therapy response were investigated. RESULTS: A total of 448 PWA were included (29% female, median (IQR) age = 54 (46-62) years, median (IQR) time post-onset = 11 (6-20) months) with 12% in the early subacute, 15% in the late subacute and 74% in the chronic phase of aphasia. The immediate responder rate was 59%. Significant improvements in all AAT subtests und subscales were observed hinting at broad effectiveness across language domains. The degree of therapy-induced improvement did not differ between the chronicity groups. Time post-onset, dosage of therapy and aphasia severity at the beginning of treatment were predictors of immediate treatment response. DISCUSSION: Intensive therapy protocols for aphasia after stroke are yielding substantial responder rates in a routine clinical setting including a wide range of patients.
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OBJECTIVE: The aims of the study were to (1) characterize the findings of flexible endoscopic evaluation of swallowing (FEES) in stroke patients undergoing mechanical thrombectomy (MT); (2) analyse the screening performance of the Standardized Swallowing Assessment (SSA); and (3) study the impact of FEES-defined dysphagia on 3-month outcomes. METHODS: This single-centre study was based on a local registry of consecutive acute ischaemic stroke patients undergoing MT during a 1-year period. Patients received FEES within 5 days of admission regardless of the result of dysphagia screening. We compared baseline demographic and clinical characteristics of patients with and without FEES-defined dysphagia. We collected 3-month modified Rankin Scale (mRS) and individual index values of the European Quality of Life 5 Dimensions (EQ-5D-iv). Using univariable and multivariable regression analyses we predicted 3-month outcomes for presence of dysphagia and for FEES-defined dysphagia severity. RESULTS: We included 137 patients with a median age of 74 years, 43.1% were female, median NIHSS was 12 and successful recanalization was achieved in 92.7%. Stroke-associated pneumonia occurred in 8% of patients. FEES-defined dysphagia occurred in 81% of patients. Sensitivity of the SSA as a dysphagia screening was 67%. Presence of dysphagia and increasing severity of dysphagia were independently associated with increasing 3-month mRS score. Increasing dysphagia severity dysphagia was independently associated with lower EQ-5D-iv. INTERPRETATION: Early FEES-defined dysphagia occurs in four in every five patients undergoing MT. SSA has a suboptimal dysphagia screening performance. Presence of dysphagia and increasing dysphagia severity predict worse functional outcome and worse health-related quality-of-life.
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Isquemia Encefálica , Trastornos de Deglución , Accidente Cerebrovascular , Humanos , Femenino , Anciano , Masculino , Deglución , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/etiología , Isquemia Encefálica/complicaciones , Calidad de Vida , Trombectomía/efectos adversosRESUMEN
INTRODUCTION: Mechanical thrombectomy (MT) is an established treatment approach in acute ischemic stroke patients with large vessel occlusion (LVO). Recent studies suggest that the prevalence of dysphagia and pneumonia risk is increased in this patient population. The aim of this study was to systematically evaluate the prevalence, predictors, and influence of neurogenic dysphagia for 3-month outcome in a large population of patients receiving MT and to elucidate the relationship between dysphagia, stroke-associated pneumonia (SAP) and medium-term functional outcome. MATERIALS AND METHODS: Data of a prospective collected registry of patients with LVO and MT between 2016 and 2019 were analyzed retrospectively. Binary logistic regression was carried out to determine predictors for dysphagia and 3-month outcome as measured by the modified Rankin Scale, respectively. A mediation analysis was performed to investigate the mediating influence of intercurrent SAP. RESULTS: A total of 567 patients were included in the study. Mean age was 73.4 years, 47.8% of the patients were female, and median NIHSS was 15.0. The prevalence of dysphagia was 75.1% and 23.3% of all patients developed SAP. In the regression analysis, dysphagia was one of the main independent predictors for poor functional outcome at 3 months. The mediator analysis revealed that the effect of dysphagia on the functional outcome at 3 months was not mediated by the occurrence of SAP. DISCUSSION: The prevalence of dysphagia is high and exerts both negative short- and medium-term effects on patients with large vessel occlusion who undergo MT.
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Isquemia Encefálica , Trastornos de Deglución , Accidente Cerebrovascular Isquémico , Neumonía , Accidente Cerebrovascular , Humanos , Femenino , Anciano , Masculino , Accidente Cerebrovascular Isquémico/etiología , Estudios Retrospectivos , Estudios Prospectivos , Trastornos de Deglución/epidemiología , Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Trombectomía/efectos adversos , Resultado del Tratamiento , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/epidemiología , Neumonía/etiología , Isquemia Encefálica/complicaciones , Isquemia Encefálica/epidemiologíaRESUMEN
BACKGROUND: Several non-motor symptoms are present in Parkinson's disease (PD), including increasing prevalence rates of cognitive impairment during disease progression. Due to its multifaceted nature, PD management involves pharmacotherapy and non-pharmacotherapies, ideally in a multidisciplinary manner. Evidence regarding the impact of multidisciplinary interventions on motor and non-motor symptoms, as well as its impact on quality of life and daily activities of living, is limited. METHODS: The aim of this real-life exploratory study was to investigate the effectiveness of a three-week clinical multidisciplinary Parkinson complex therapy (Parkinson-Komplexbehandlung, PKB), which is available as standard care for PD in the German health care system. Especially, the effect of neuropsychological attention training of 40 patients with PD was analyzed concerning their impact on motor abilities (UPDRS-III ON state), cognitive profiles and reported depressive symptoms and psychosocial function. RESULTS: Neuropsychological data showed an improvement in response inhibition after intervention (z = - 2.611, p = 0.009). Additionally, improvements in verbal memory (z = - 2.318, p = 0.020), motor functions (UPDRS-III-score; z = - 5.163, p < 0.001) and reduction in depression symptoms (BDI-II) (z = - 2.944, p = 0.003) were also present. CONCLUSIONS: Patients with PD benefited from this multidisciplinary Parkinson complex therapy in terms of improved cognitive functioning, including attention and verbal learning, motor symptoms and emotional well-being.
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INTRODUCTION: Frailty is a disorder of multiple physiological systems impairing the capacity of the organism to cope with insult or stress. It is associated with poor outcomes after acute illness. Our aim was to study the impact of frailty on the functional outcome of patients with acute ischemic stroke (AIS) submitted to endovascular stroke treatment (EST). METHODS: We performed a retrospective study of patients with AIS of the anterior circulation submitted to EST between 2012 and 2017, based on a prospectively collected local registry of consecutive patients. The Hospital Frailty Risk Score (HFRS) at discharge was calculated for each patient. We compared groups of patients with and without favourable 3-month outcome after index AIS (modified Rankin Scale 0-2 and 3-6, respectively). A multivariable logistic regression model was used to identify variables independently associated with favourable 3-month outcome. Diagnostic test statistics were used to compare HFRS with other prognostic scores for AIS. RESULTS: We included 489 patients with median age 75.6 years (interquartile range [IQR] = 65.3-82.3) and median NIHSS 15 (IQR = 11-19). About 29.7% presented a high frailty risk (HFRS >15 points). Patients with favourable 3-month outcome presented lower HFRS and lower prevalence of high frailty risk. High frailty risk was independently associated with decreased likelihood of favourable 3-month outcome (adjusted odds ratio = 0.48, 95% confidence interval = 0.26-0.89). Diagnostic performances of HFRS and other prognostic scores (THRIVE and PRE scores, SPAN-100 index) for outcome at 3-months were similar. DISCUSSION: Frailty is an independent predictor of outcome in AIS patients submitted to EST.
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Isquemia Encefálica , Fragilidad , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Anciano , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiología , Isquemia Encefálica/terapia , Fragilidad/diagnóstico , Fragilidad/epidemiología , Fragilidad/terapia , Humanos , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Dysphagia is one of the most common and important complications in Huntington disease (HD), frequently leading to aspiration pneumonia and mortality. Objective estimates of prevalence using instrumental diagnostics and data on neural correlates of dysphagia in HD are scarce or lacking entirely. Similarly, its correlation with other clinical markers is still not fully known. We aimed at defining clinical risk factors and neural correlates for compromised swallowing safety in HD more precisely. METHODS: Thirty-four HD subjects (16 female, Shoulson & Fahn Stage I-IV, two premanifest) underwent a full clinical-neurological examination including the cranial nerves, the Unified Huntington's Disease Rating Scale total motor score, and the Mini-Mental State Examination. Fiberoptic endoscopic evaluation of swallowing (FEES) was performed by a trained speech and language therapist. Twenty-six subjects additionally underwent a high-resolution anatomical magnetic resonance imaging (MRI) scan (T1, 3-T Siemens Prisma). Moreover, we correlated clinical and atrophy (MRI) measures with swallowing safety levels as judged by the validated Penetration-Aspiration Scale. RESULTS: FEES showed penetration or aspiration in 70.6%. Using partial correlation, no significant correlations were found between swallowing safety and any of the clinical markers after correcting for disease duration and CAG repeat length. Voxel-based morphometry demonstrated atrophy associated with compromised swallowing safety in a network of parietothalamocerebellar areas related to sensorimotor communication, notably excluding striatum. CONCLUSIONS: Our results characterise dysphagia in HD as a disorder of communication between sensory and motor networks involved in swallowing. This finding and high rates of silent aspiration argue in favor of instrumental swallowing evaluation early in the disease.
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Trastornos de Deglución , Enfermedad de Huntington , Deglución , Trastornos de Deglución/diagnóstico por imagen , Trastornos de Deglución/etiología , Femenino , Sustancia Gris , Humanos , Enfermedad de Huntington/complicaciones , Enfermedad de Huntington/diagnóstico por imagen , Imagen por Resonancia MagnéticaRESUMEN
INTRODUCTION: Neurogenic dysphagia defines swallowing disorders caused by diseases of the central and peripheral nervous system, neuromuscular transmission, or muscles. Neurogenic dysphagia is one of the most common and at the same time most dangerous symptoms of many neurological diseases. Its most important sequelae include aspiration pneumonia, malnutrition and dehydration, and affected patients more often require long-term care and are exposed to an increased mortality. Based on a systematic pubmed research of related original papers, review articles, international guidelines and surveys about the diagnostics and treatment of neurogenic dysphagia, a consensus process was initiated, which included dysphagia experts from 27 medical societies. RECOMMENDATIONS: This guideline consists of 53 recommendations covering in its first part the whole diagnostic spectrum from the dysphagia specific medical history, initial dysphagia screening and clinical assessment, to more refined instrumental procedures, such as flexible endoscopic evaluation of swallowing, the videofluoroscopic swallowing study and high-resolution manometry. In addition, specific clinical scenarios are captured, among others the management of patients with nasogastric and tracheotomy tubes. The second part of this guideline is dedicated to the treatment of neurogenic dysphagia. Apart from dietary interventions and behavioral swallowing treatment, interventions to improve oral hygiene, pharmacological treatment options, different modalities of neurostimulation as well as minimally invasive and surgical therapies are dealt with. CONCLUSIONS: The diagnosis and treatment of neurogenic dysphagia is challenging and requires a joined effort of different medical professions. While the evidence supporting the implementation of dysphagia screening is rather convincing, further trials are needed to improve the quality of evidence for more refined methods of dysphagia diagnostics and, in particular, the different treatment options of neurogenic dysphagia. The present article is an abridged and translated version of the guideline recently published online ( https://www.awmf.org/uploads/tx_szleitlinien/030-111l_Neurogene-Dysphagie_2020-05.pdf ).
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Spastic impaired limb function is a frequent result of brain lesions. Although its assessment is important for clinical and therapeutical management, it still lacks an objective measure to quantify the functionality of the affected limb. The present paper reports a procedure based on the muscular activation recorded by Surface Electromyography (sEMG), which enables the assessment of the degree of spastic impairment. 15 healthy subjects and 7 patients with impaired upper limb function due to spasticity were included in the study. SEMG was recorded from the biceps and brachioradialis during active elbow extension at different movement velocities. The spastic impairment was clinically assessed by the Tardieu-Test and the Wolf Motor Function Test. Results of the clinical assessment and parameter values quantifying the muscular activation at different joint positions and movement velocities have been set in relation to one another. The results show that spastic impairment leads to a changed correlation between the muscular activation and movement velocity as well as to a changed inter-muscular co-ordination of biceps and brachioradialis. These changes, reflected in the sEMG, can be quantified by 5 newly introduced parameters. This way could allow the assessment of spastic impairment in the context of functional everyday tasks, for the first-time.
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Movimiento , Espasticidad Muscular/fisiopatología , Músculo Esquelético/fisiología , Algoritmos , Brazo/fisiopatología , Fenómenos Biomecánicos , Parálisis Cerebral/fisiopatología , Codo/fisiopatología , Articulación del Codo/fisiopatología , Electromiografía , Diseño de Equipo , Antebrazo/fisiopatología , Humanos , Procesamiento de Señales Asistido por Computador , Accidente Cerebrovascular/fisiopatologíaRESUMEN
Speaker attribution and labeling of single channel, multi speaker audio files is an area of active research, since the underlying problems have not been solved satisfactorily yet. This especially holds true for non-standard voices and speech, such as children and impaired speakers. Being able to perform speaker labelling of pathological speech would potentially enable the development of computer assisted diagnosis and treatment systems and is thus a desirable research goal. In this manuscript we investigate on the applicability of embeddings of audio signals, in the form of time and frequency-band based segments, into arbitrary vector spaces on diarization of pathological speech. We focus on modifying an existing embedding estimator such that it can be used for diarization. This is mainly done via clustering the time and frequency band dependant vectors and subsequently performing a majority vote procedure on all frequency dependent vectors of the same time segment to assign a speaker label. The result is evaluated on recordings of interviews of aphasia patients and language therapists. We demonstrate general applicability, with error rates that are close to what has been previously achieved in diarizing children's speech. Additionally, we propose to enhance the processing pipelines with smoothing and a more sophisticated, energy based, voting scheme.
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Afasia , Análisis por Conglomerados , Habla , Afasia/diagnóstico , Niño , Humanos , LenguajeRESUMEN
BACKGROUND: At present, the flexible endoscopic evaluation of swallowing (FEES) is one of the most commonly used methods for the objective assessment of swallowing. This multicenter trial prospectively collected data on the safety of FEES and also assessed the impact of this procedure on clinical dysphagia management. METHODS: Patients were recruited in 23 hospitals in Germany and Switzerland from September 2014 to May 2017. Patient characteristics, professional affiliation of the FEES examiners (physicians or speech and language therapists), side-effects and cardiorespiratory parameters, severity of dysphagia and clinical consequences of FEES were documented. RESULTS: 2401 patients, mean age 69.8 (14.6) years, 42.3% women, were included in the FEES-registry. The most common main diagnosis was stroke (61%), followed by Parkinson's disease (6.5%). FEES was well tolerated by patients. Complications were reported in 2% of examinations, were all self-limited and resolved without sequelae and showed no correlation to the endoscopist's previous experience. In more than 50% of investigations FEES led to changes of feeding strategies, in the majority of cases an upgrade of oral diet was possible. DISCUSSION: This study confirmed that FEES, even when performed by less experienced clinicians is a safe and well tolerated procedure and significantly impacts on the patients' clinical course. Implementation of a FEES-service in different clinical settings may improve dysphagia care. TRIAL REGISTRATION: ClinicalTrials.gov NCT03037762, registered January 31st 2017.
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Suicide is a leading cause of death in Huntington's disease (HD), following pneumonia. Up to one-fifth of individuals with HD report suicidal ideation. Identifying the risk factors of suicidal ideation in this clinical population is thus pivotal. Here, we review the literature on prevalence rates and risk factors of suicidal ideation in premanifest and manifest patients and re-evaluate them using the largest currently existing clinical dataset from the ongoing observational study "Enroll-HD" (N = 5709). Large scale studies yielded important insights regarding suicidal ideation in HD. However, estimated prevalence rates vary among studies and risk factors are still poorly understood. According to the Enroll-HD data, pre- and manifest disease stages are associated with current (5.8-10%) and a history of suicidal ideation (18.6-30.9%). Throughout the course of HD, a history of suicidal ideation and the presence of depressive symptoms were strongly associated with current suicidal ideation. However, while for premanifest individuals, socio-demographics and activities of daily living appear to be important, in manifest patients, suicidal ideation is more closely linked to anxiety, irritability, psychosis, and apathy. These results highlight the importance of treating depressive symptoms in patients with HD and addressing potential suicidal ideation during clinical monitoring. The relevance of risk factors may differ among premanifest and manifest patients.
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Enfermedad de Huntington/epidemiología , Enfermedad de Huntington/psicología , Ideación Suicida , Humanos , Factores de RiesgoRESUMEN
BACKGROUND: Dysphagia after stroke is common, especially in severely affected patients who have had a tracheotomy. In a pilot trial, pharyngeal electrical stimulation (PES) improved swallowing function in this group of patients. We aimed to replicate and extend this single-centre experience. METHODS: We did a prospective, single-blind, randomised controlled trial across nine sites (seven acute care hospitals, two rehabilitation facilities) in Germany, Austria, and Italy. Patients with recent stroke who required tracheotomy were randomly assigned to receive 3 days of either PES or sham treatment (1:1). All patients had the stimulation catheter inserted; sham treatment was applied by connecting the PES base station to a simulator box instead of the catheter. Randomisation was done via a computerised interactive system (stratified by site) in blocks of four patients per site. Patients and investigators applying PES were not masked. The primary endpoint was assessed by a separate investigator at each site who was masked to treatment assignment. The primary outcome was readiness for decannulation 24-72 h after treatment, assessed using fibreoptic endoscopic evaluation of swallowing and based on a standardised protocol, including absence of massive pooling of saliva, presence of one or more spontaneous swallows, and presence of at least minimum laryngeal sensation. We planned a sequential statistical analysis of superiority for the primary endpoint. Interim analyses were to be done after primary outcome data were available for 50 patients (futility), 70 patients, and every additional ten patients thereafter, up to 140 patients. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN18137204. FINDINGS: From May 29, 2015, to July 5, 2017, of 81 patients assessed, 69 patients from nine sites were randomly assigned to receive PES (n=35) or sham (n=34) treatment. Median onset to randomisation time was 28 days (IQR 19-41; PES 28 [20-49]; sham 28 [18-40]). The Independent Data and Safety Monitoring Board recommended that the trial was stopped early for efficacy after 70 patients had been recruited and primary endpoint data for 69 patients were available. This decision was approved by the steering committee. More patients were ready for decannulation in the PES group (17 [49%] of 35 patients) than in the sham group (three [9%] of 34 patients; odds ratio [OR] 7·00 [95% CI 2·41-19·88]; p=0·0008). Adverse events were reported in 24 (69%) patients in the PES group and 24 (71%) patients in the sham group. The number of patients with at least one serious adverse event did not differ between the groups (ten [29%] patients in the PES group vs eight [23%] patients in the sham group; OR 1·30 [0·44-3·83]; p=0·7851). Seven (20%) patients in the PES group and three (9%) patients in the sham group died during the study period (OR 2·58 [0·61-10·97]; p=0·3059). None of the deaths or serious adverse events were judged to be related to PES. INTERPRETATION: In patients with stroke and subsequent tracheotomy, PES increased the proportion of patients who were ready for decannulation in this study population, many of whom received PES within a month of their stroke. Future trials should confirm whether PES is beneficial in tracheotomised patients who receive stimulation similarly early after stroke and explore its effects in other cohorts. FUNDING: Phagenesis Ltd.
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Trastornos de Deglución/terapia , Terapia por Estimulación Eléctrica/métodos , Evaluación de Resultado en la Atención de Salud , Faringe , Accidente Cerebrovascular/terapia , Traqueotomía/efectos adversos , Anciano , Cateterismo , Trastornos de Deglución/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Método Simple Ciego , Accidente Cerebrovascular/complicacionesRESUMEN
Biomarkers in whichever modality are tremendously important in diagnosing of disease, tracking disease progression and clinical trials. This applies in particular for disorders with a long disease course including pre-symptomatic stages, in which only subtle signs of clinical progression can be observed. Magnetic resonance imaging (MRI) biomarkers hold particular promise due to their relative ease of use, cost-effectiveness and non-invasivity. Studies measuring resting-state functional MR connectivity have become increasingly common during recent years and are well established in neuroscience and related fields. Its increasing application does of course also include clinical settings and therein neurodegenerative diseases. In the present review, we critically summarise the state of the literature on resting-state functional connectivity as measured with functional MRI in neurodegenerative disorders. In addition to an overview of the results, we briefly outline the methods applied to the concept of resting-state functional connectivity. While there are many different neurodegenerative disorders cumulatively affecting a substantial number of patients, for most of them studies on resting-state fMRI are lacking. Plentiful amounts of papers are available for Alzheimer's disease (AD) and Parkinson's disease (PD), but only few works being available for the less common neurodegenerative diseases. This allows some conclusions on the potential of resting-state fMRI acting as a biomarker for the aforementioned two diseases, but only tentative statements for the others. For AD, the literature contains a relatively strong consensus regarding an impairment of the connectivity of the default mode network compared to healthy individuals. However, for AD there is no considerable documentation on how that alteration develops longitudinally with the progression of the disease. For PD, the available research points towards alterations of connectivity mainly in limbic and motor related regions and networks, but drawing conclusions for PD has to be done with caution due to a relative heterogeneity of the disease. For rare neurodegenerative diseases, no clear conclusions can be drawn due to the few published results. Nevertheless, summarising available data points towards characteristic connectivity alterations in Huntington's disease, frontotemporal dementia, dementia with Lewy bodies, multiple systems atrophy and the spinocerebellar ataxias. Overall at this point in time, the data on AD are most promising towards the eventual use of resting-state fMRI as an imaging biomarker, although there remain issues such as reproducibility of results and a lack of data demonstrating longitudinal changes. Improved methods providing more precise classifications as well as resting-state network changes that are sensitive to disease progression or therapeutic intervention are highly desirable, before routine clinical use could eventually become a reality.
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Biomarcadores , Mapeo Encefálico , Imagen por Resonancia Magnética , Vías Nerviosas/fisiopatología , Enfermedades Neurodegenerativas/patología , Humanos , Enfermedades Neurodegenerativas/fisiopatología , Descanso/fisiologíaRESUMEN
Recent evidence suggests that a period of sleep after a motor learning task is a relevant factor for memory consolidation. However, it is yet open whether this also holds true for language-related learning. Therefore, the present study compared the short- and long-term effects of a daytime nap, rest, or an activity task after vocabulary learning on learning outcome. Thirty healthy subjects were divided into three treatment groups. Each group received a pseudo-word learning task in which pictures of monsters were associated with unique pseudo-word names. At the end of the learning block a first test was administered. Then, one group went for a 90-min nap, one for a waking rest period, and one for a resting session with interfering activity at the end during which a new set of monster names was to be learned. After this block, all groups performed a first re-test of the names that they initially learned. On the morning of the following day, a second re-test was administered to all groups. The nap group showed significant improvement from test to re-test and a stable performance onto the second re-test. In contrast, the rest and the interference groups showed decline in performance from test to re-test, with persistently low performance at re-test 2. The 3 (GROUP) × 3 (TIME) ANOVA revealed a significant interaction, indicating that the type of activity (nap/rest/interfering action) after initial learning actually had an influence on the memory outcome. These data are discussed with respect to translation to clinical settings with suggestions for improvement of intervention outcome after speech-language therapy if it is followed by a nap rather than interfering activity.
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Atención Ambulatoria/métodos , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/enfermería , Evaluación en Enfermería , Diagnóstico de Enfermería , Anciano , Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Diagnóstico Diferencial , Humanos , Psicoterapia/métodos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/enfermería , Accidente Cerebrovascular/terapiaRESUMEN
OBJECTIVE: Friedreich's ataxia (FRDA) is a spinocerebellar degenerative disorder, in which cognitive deficits are sparsely explored. In this behavioral and multimodal magnetic resonance imaging (MRI) study, we investigated the neurocognitive profile and cortico-cerebellar dysfunctions underlying executive functioning in individuals with FRDA. METHODS: 22 FRDA patients and 22 controls were clinically and neuropsychologically examined. Fifteen of each underwent structural and functional MRI using a verbal-fluency task with phonemic and semantic conditions. Gray (GM) and white matter (WM) alterations were assessed by means of voxel-based morphometry and diffusion-tensor imaging. RESULTS: The neuropsychological profile demonstrated deficits in verbal fluency, working memory and social cognition. Functional MRI data showed most pronounced group-differences in phonemic fluency with patients exhibiting enhanced activity in the cerebellum (VI, Crus I), fronto-insular, premotor and temporo-occipital regions. The semantic condition only revealed reduced activity in the anterior cerebellum; for overt speech, we found increased activity in the motor cortex. Functional connectivity-analysis showed higher co-activation within cerebellar and cortical regions, respectively, and impaired interregional coupling between the cerebellum and fronto-insular cortex for phonemic processing, which was also related to poorer task performance. GM reduction in FRDA was mainly found in lobule VI, whereas WM degeneration was more pronounced including brainstem, cerebellum, and cortex. Decreased cerebellar GM was associated with enhanced activity in the fronto-insular cortex, while loss of WM integrity may translate cortico-cerebellar pathway disruptions. INTERPRETATION: The pattern of increased neural response with both cerebellar and cortical involvement underlying executive functioning indicates functional reorganization driven by disease-related structural damage in FRDA.