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.

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.

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.

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.

Neural Correlates of Oral Stereognosis-An fMRI Study.

Oral stereognosis is the ability to recognize, discriminate and localize a bolus in the oral cavity. Clinical observation indicates deficits in oral stereognosis in patients with vascular or neurodegenerative diseases particularly affecting the parietal lobes. However, the precise neural representation of oral stereognosis remains unclear whereas the neural network of manual stereognosis has already been identified. We hypothesize that oral and manual stereognosis share common neuronal substrates whilst also showing somatotopic distribution. Functional magnetic resonance images (fMRI; Siemens Prisma 3 T) from 20 healthy right-handed participants (11 female; mean age 25.7 years) using a cross-modal task of oral and manual spatial object manipulation were acquired. Data were analyzed using FSL software using a block design and standard analytical and statistical procedures. A conjunction analysis targeted the common neuronal substrate for stereognosis. Activations associated with manual and oral stereognosis were found in partially overlapping fronto-parietal networks in a somatotopic fashion, where oral stereognosis is located caudally from manual stereognosis. A significant overlap was seen in the left anterior intraparietal sulcus. Additionally, cerebellar activations were shown particularly for the oral condition. Spatial arrangement of shaped boli in the oral cavity is associated with neuronal activity in fronto-parietal networks and the cerebellum. These findings have significant implications for clinical diagnostics and management of patients with lesions or atrophy in parietal lobule (e.g. Alzheimer's disease, stroke). More studies are required to investigate the clinical effect of damage to these areas, such as loss of oral stereognosis or an impaired oral phase.

Development of a cluster-like headache after a stent-assisted implantation of an endovascular WEB device.

After interdisciplinary consent, a male patient in his 50s received endovascular treatment of an innocent supraophthalmic aneurysm of the internal carotid artery with a WEB (woven endo bridge) device and stenting. In the medical history, a migraine with aura was reported. A week after intervention, the patient developed an ipsilateral cluster-like headache responsive to classical interventions. Inflammation of the carotid wall near the stent was demonstrated to be associated with the headaches and was responsive to steroid treatment.The presented case demonstrates that postinterventional headache comprises more headache entities than the often reported migraine and tension-type headache with a considerable impact on the patients' quality of life. The case supports the vascular hypothesis of cluster headache pathophysiology, potentially contradicting current models and assumptions.

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.

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.

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.

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 ).

Time on previous renal replacement therapy is associated with worse outcomes of COVID-19 in a regional cohort of kidney transplant and dialysis patients.

ABSTRACT: Chronic renal replacement therapy by either a kidney transplant (KTX) or hemodialysis (HD) predisposes patients to an increased risk for adverse outcomes of COVID-19. However, details on this interaction remain incomplete. To provide further characterization, we undertook a retrospective observational cohort analysis of the majority of the hemodialysis and renal transplant population affected by the first regional outbreak of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) in Germany. In a region of 250,000 inhabitants we identified a total of 21 cases with SARS-CoV-2 among 100 KTX and 260 HD patients, that is, 7 KTX with COVID-19, 14 HD with COVID-19, and 3 HD with asymptomatic carrier status. As a first observation, KTX recipients exhibited trends for a higher mortality (43 vs 18%) and a higher proportion of acute respiratory distress syndrome (ARDS) (57 vs 27%) when compared to their HD counterparts. As a novel finding, development of ARDS was significantly associated with the time spent on previous renal replacement therapy (RRT), defined as the composite of dialysis time and time on the transplant (non-ARDS 4.3 vs ARDS 10.6 years, P = .016). Multivariate logistic regression analysis showed an OR of 1.7 per year of RRT. The association remained robust when analysis was confined to KTX patients (5.1 vs 13.2 years, P = .002) or when correlating the time spent on a renal transplant alone (P = .038). Similarly, longer RRT correlated with death vs survival (P = .0002). In conclusion our data suggest renal replacement vintage as a novel risk factor for COVID-19-associated ARDS and death. The findings should be validated by larger cohorts.

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.

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.

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.

Risk factors of suicidal ideation in Huntington's disease: literature review and data from Enroll-HD.

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.

Pharyngeal electrical stimulation for early decannulation in tracheotomised patients with neurogenic dysphagia after stroke (PHAST-TRAC): a prospective, single-blinded, randomised trial.

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.

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.

Mortality and cardiorespiratory complications in trochanteric femoral fractures: a ten year retrospective analysis.

PURPOSE: Despite intense research and innovations in peri-operative management, a high mortality rate and frequent systemic complications in trochanteric femoral fractures persist. The aim of the present study was to identify predictive factors for mortality and cardio-respiratory complications after different treatment methods in a ten year period at a level I trauma centre. METHODS: Retrospectively, all patients above 60 years of age with trochanteric femoral fracture between January 2000 and May 2011 were analyzed at a level I trauma centre. Demographic variables, comorbidities, and data regarding the surgical procedures, including required transfusions and post-operative complications, were evaluated, and the in-hospital mortality was recorded. The grade of osteoporosis was classified radiographically using the Singh index. RESULTS: The in-hospital mortality rate was 8.2% among 437 patients (male/female ratio = 110/327, mean age = 81 years) with extramedullary open (n = 144), intramedullary (n = 166), and extramedullary minimally invasive (n = 125) procedures. Significant influential factors on in-hospital mortality were identified with binary logistic regression analysis: an age of ≥90 years (P = 0.011), male sex (P = 0.003), a high American Society of Anesthesiologists (ASA) grade (3-5, P = 0.042), and a high osteoporosis grade (Singh index 3-1, P = 0.011). A total of 21.5% of the study population suffered cardio-respiratory complications post-operatively. The specific mortality was 28.7% (P < 0.001), which was influenced by a high ASA grade (3-5, P = 0.002) and a high transfusion rate (P = 0.004). Minimally invasive locked plating was associated with increased cardio-respiratory complications (P = 0.031). CONCLUSIONS: This study identified high patient age, distinctive comorbidities, male sex, and high osteoporosis grade as significant risk factors for increased in-hospital mortality in the treatment of trochanteric femoral fractures. Furthermore, high ASA grade and a liberal transfusion regime led to an increased incidence of cardio-respiratory complications. Patient-specific characteristics, especially osteoporosis grade and pre-existing medical conditions, may assist in the identification of high-risk patients and allow a patient-specific geriatric co-management plan.