Blood-based frailty index in patients with acute ischemic stroke undergoing endovascular treatment.

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.

Clinical predictors and neural correlates for compromised swallowing safety in Huntington disease.

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.

Frailty is an outcome predictor in patients with acute ischemic stroke receiving endovascular treatment.

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.

Altered resting-state connectivity in Huntington's disease.

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Using resting-state fMRI (rs-fMRI) we investigated the functional integrity of resting-state networks (RSN) in HD. 17 HD and 19 matched control participants were examined at a 3 Tesla MR scanner. After controlling for structural degeneration by means of voxel-based morphometry, task-free rs-fMRI data were analyzed using Independent Component Analysis (ICA) and a dual-regression approach in the context of genetic and clinical parameters. Further, we evaluated HD-related differences in interregional connectivity between networks. RSN analysis showed a significant increase in intrinsic functional connectivity in the HD sample compared with controls, including the thalamus, striatum, prefrontal, premotor, and parietal maps. A subset of the Default Mode Network (DMN) was also affected. In the HD cohort, motor impairment correlated with higher network connectivity in mainly motor and parietal cortices. Deteriorating total functional capacity was additionally associated with higher connectivity in the striatum, thalamus, insular and frontal areas. This pattern of increased activity in intrinsic functional networks might suggest a reduced ability of intra-network differentiation with clinical disease progression in HD. Finally, results showed reduced long-range connectivity between parietal ICA components in HD compared to controls, indicating impaired functional coupling between interregional networks in HD. Our data demonstrates that functional connectivity is profoundly altered in HD, both within and between RSN. Rs-fMRI analysis may provide additional valuable insights into neuronal dysfunctions beyond HD-related structural degeneration and disruptions of functional circuits in HD.

Swallowing muscle mass contributes to post-stroke dysphagia in ischemic stroke patients undergoing mechanical thrombectomy.

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.

Early flexible endoscopic evaluation of swallowing after mechanical thrombectomy in stroke patients.

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.

Success rates of intensive aphasia therapy: real-world data from 448 patients between 2003 and 2020.

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.

The relationship between neurogenic dysphagia, stroke-associated pneumonia and functional outcome in a cohort of ischemic stroke patients treated with mechanical thrombectomy.

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.

Increased brain tissue sodium concentration in Huntington's Disease - a sodium imaging study at 4 T.

The neuropathological hallmark of the autosomal dominantly inherited, neurodegenerative disorder Huntington's disease is progressive striatal loss starting several years prior to symptom manifestation. Magnetic resonance (MR) imaging has been widely used to detect altered structure in premanifest and early Huntington's disease. Given that neurodegeneration is likely preceded by substantial neuronal dysfunction, we used in vivo sodium MR imaging, which has been shown to be sensitive to cell death and viability, to investigate cellular and metabolic integrity of Huntington's disease brain tissue. We studied a total of thirteen healthy controls and thirteen Huntington's disease gene carriers (11 manifest and 2 premanifest). The manifest Huntington's disease group was subdivided into stages 1 and 2 according to their Total Functional Capacity scores. Clinical total motor and cognitive scores, as well as calibrated sodium and T1-weighted MR images were obtained with a 4 T Siemens MR scanner. Sodium images were acquired by means of a constant time imaging technique with an ultra-short "echo time". T1-weighted MR images were further analysed with voxel-based morphometry. The absolute total sodium concentration and grey matter values were measured in several Huntington's disease-specific and also non-specific areas. Statistical analysis of variance and Pearson correlation were applied. In Huntington's disease subjects, we found an increase of total sodium concentration of the entire brain compared to controls. Increased total sodium concentration values were found in structurally affected, but also in some non-affected, regions. The highest total sodium concentration values were found in the bilateral caudate, which was associated with caudate grey matter atrophy and CAG repeat length. In all Huntington's disease subjects we further found a profound increase of total sodium concentration in the putamen, pallidum, thalamus, hippocampus, insula, precuneus and occipital cortex compared to controls. No change of total sodium concentration was observed in the amygdala, pre- and postcentral gyrus, frontal and temporal cortices or in the cerebellum. This is the first in vivo sodium MR imaging study carried out on a 4 T MR scanner in Huntington's disease gene carriers demonstrating a significant enhancement in sodium concentration in the bilateral striatum, a key region in Huntington's disease, and also in other disease-related atrophic areas. Sodium MR imaging may provide a deeper insight into the pathophysiological mechanisms of tissue degeneration in Huntington's disease, presenting potential to detect changes preceding neurodegeneration.

Why cognitive training is important for the health status in Parkinson's disease: preliminary evidence from a clinical three-weeks multidisciplinary intervention.

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.

Altered motor network activation and functional connectivity in adult Tourette's syndrome.

Tourette's syndrome (TS) is a developmental neuropsychiatric disorder characterized by motor and vocal tics as well as psychiatric comorbidities. Disturbances of the fronto-striatal-thalamic pathways responsible for motor control and impulse inhibition have been previously described in other studies. Although differences in motor performance are well recognized, imaging data elucidating the neuronal correlates are scarce. Here, we examined 19 adult TS patients (13 men, aged 22-52 years, mean = 34.3 years) and 18 age- and sex-matched controls (13 men, aged 24-57 years, mean = 37.6 years) in a functional magnetic resonance imaging study at 1.5 T. We corrected for possible confounds introduced by tics, motion, and brain-structural differences as well as age, sex, comorbidities, and medication. Patients and controls were asked to perform a sequential finger-tapping task using their right, left, and both hands, respectively. Task performance was monitored by simultaneous MR-compatible video recording. Although behavioral data obtained during scanning did not show significant differences across groups, we observed differential neuronal activation patterns depending on both handedness (dominant vs. nondominant) and tapping frequency in frontal, parietal, and subcortical areas. When controlling for open motor performance, a failure of deactivation in easier task conditions was found in the subgenual cingulate cortex in the TS patients. In addition, performance-related functional connectivity of lower- and higher-order motor networks differed between patients and controls. In summary, although open performance was comparable, patients showed different neuronal networks and connectivity patterns when performing increasingly demanding tasks, further illustrating the impact of the disease on the motor system.

Diagnosis and treatment of neurogenic dysphagia - S1 guideline of the German Society of Neurology.

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 ).

Altered amygdala functional connectivity in adult Tourette's syndrome.

Tourette's syndrome (TS) is a developmental neuropsychiatric disorder characterized by motor and vocal tics as well as psychiatric comorbidities. Recently, differences in maturation of cortical networks using functional connectivity metrics have been described for this disorder. However, adult data on subcortical networks are scarce. In particular, the connectivity of the amygdala, for which a role in the pathophysiology of TS has been established, has not been examined so far. We studied 15 adult TS patients (11 male, aged 30.4 ± 9.7y) and 15 age- and sex-matched controls (11 male, aged 32.0 ± 9.3y) in a functional magnetic resonance imaging study at 1.5T using a simple motor task. We corrected for possible confounds introduced by tics, motion and brain-structural differences as well as age, sex, and medication. Task performance was monitored by simultaneous MR-compatible video-recording. Data were analyzed using an independent component approach sensitive to functional connectivity patterns. A stable component comprising both amygdalae could be identified across all subjects. Additionally, we observed a highly significant increase in coupling between/within amygdalae in the TS group when compared to controls, although behavioral data obtained during scanning did not show significant differences. These findings are expected to add to our understanding of the functional architecture of Tourette's syndrome.

Evaluation of Deep Clustering for Diarization of Aphasic Speech.

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.

Introduction of a procedure to objectively quantify spastic movement impairment during freely performed voluntary movements.

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.

Safety and clinical impact of FEES - results of the FEES-registry.

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.

Proteome analysis of human substantia nigra in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the most common neurodegenerative disorder involving the motor system. Although not being the only region involved in PD, affection of the substantia nigra and its projections is responsible for some of the most debilitating features of the disease. To further advance a comprehensive understanding of nigral pathology, we conducted a tissue based comparative proteome study of healthy and diseased human substantia nigra. RESULTS: The gross number of differentially regulated proteins in PD was 221. In total, we identified 37 proteins, of which 16 were differentially expressed. Identified differential proteins comprised elements of iron metabolism (H-ferritin) and glutathione-related redox metabolism (GST M3, GST P1, GST O1), including novel redox proteins (SH3BGRL). Additionally, many glial or related proteins were found to be differentially regulated in PD (GFAP, GMFB, galectin-1, sorcin), as well as proteins belonging to metabolic pathways sparsely described in PD, such as adenosyl homocysteinase (methylation), aldehyde dehydrogenase 1 and cellular retinol-binding protein 1 (aldehyde metabolism). Further differentially regulated proteins included annexin V, beta-tubulin cofactor A, coactosin-like protein and V-type ATPase subunit 1. Proteins that were similarly expressed in healthy or diseased substantia nigra comprised housekeeping proteins such as COX5A, Rho GDI alpha, actin gamma 1, creatin-kinase B, lactate dehydrogenase B, disulfide isomerase ER-60, Rab GDI beta, methyl glyoxalase 1 (AGE metabolism) and glutamine synthetase. Interestingly, also DJ-1 and UCH-L1 were expressed similarly. Furthermore, proteins believed to serve as internal standards were found to be expressed in a constant manner, such as 14-3-3 epsilon and hCRMP-2, thus lending further validity to our results. CONCLUSION: Using an approach encompassing high sensitivity and high resolution, we show that alterations of SN in PD include many more proteins than previously thought. The results point towards a heterogeneous aetiopathogenesis of the disease, including alterations of GSH-related proteins as well as alterations of proteins involved in retinoid metabolism, and they indicate that proteins involved in familial PD may not be differentially regulated in idiopathic Parkinson's disease.

Resting-state connectivity in neurodegenerative disorders: Is there potential for an imaging biomarker?

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.