Adjustment of oral diet based on flexible endoscopic evaluation of swallowing (FEES) in acute stroke patients: a cross-sectional hospital-based registry study.

BACKGROUND: Diagnosing dysphagia in acute stroke patients is crucial, as this comorbidity determines morbidity and mortality; we therefore investigated the impact of flexible nasolaryngeal endoscopy (FEES) in acute stroke patients. METHODS: The FEES investigation as performed in acute stroke patients treated at a large university hospital, allocated as a standard procedure for all patients suspected of dysphagia. We correlated our findings with baseline data, disability status, pneumonia, duration of hospitalisation, necessity for mechanical ventilation and treatment on the intensive care unit. The study was designed as a cross-sectional hospital-based registry. RESULTS: We investigated 152 patients. The median age was 73; 94 were male. Ischemic stroke was diagnosed in 125 patients (82.2%); 27 (17.8%) suffered intracerebral haemorrhage. Oropharyngeal dysphagia was diagnosed in 72.4% of the patients, and was associated with higher stroke severity on admission (median NIHSS 11 [IQR 6-17] vs. 7 [4-12], p = .013; median mRS 5 [IQR 4-5] vs. 4 [IQR 3-5], p = .012). Short-term mortality was higher among patients diagnosed with dysphagia (7.2% vs. 0%, p = .107). FEES examinations revealed that only 30.9% of the patients had an oral diet appropriate for their swallowing abilities. A change of oral diet was associated with a better outcome at discharge (mRS; p = .006), less need of mechanical ventilation (p = .028), shorter period of hospitalisation (p = .044), and lower rates of pneumonia (p = .007) and mortality (p = .011). CONCLUSION: Due to the inability of clinical assessments to detect silent aspiration, FEES might be better suited to identify stroke patients at risk and may contribute to a better functional outcome and lower rates of pneumonia and mortality. Our findings also point to a low awareness of dysphagia, even in a specialised stroke centre. FEES in acute stroke patients helps to adjust the oral diet for the vast majority of stroke patients (69.1%) based on their swallowing abilities, potentially avoiding severe complications.

Spasticity treatment with onabotulinumtoxin A: data from a prospective German real-life patient registry.

This study aimed at providing real-life baseline, injection and outcome data for the treatment of various forms of spasticity with onabotulinumtoxin A in Germany. Prospective data were collected in an open multicenter patient registry from 2005 until 2010, encompassing the experience of ten specialized German centers in the treatment of spasticity using onabotulinumtoxin A in 508 patients with a total of 2005 treatment sessions. Disease entities comprised spasticity following stroke (both ischemic and hemorrhagic), traumatic brain injury, multiple sclerosis, cerebral palsy, and anoxia. Sustained improvement was observed in a variety of outcome parameters including goal attainment and motor performance scores for up to five repeated injection sessions. No significant differences between disease entities or between upper and lower limb treatment were observed with regard to efficacy and safety following onabotulinumtoxin A treatment. Minor to moderate side effects were reported in <1 % of the study population. We conclude that repetitive treatment of focal and multifocal spasticity with onabotulinumtoxin A provides a safe and efficacious therapeutic strategy for patients with different disease entities of the central nervous system.

Age-related changes in oral sensitivity, taste and smell.

Oropharyngeal sensitivity plays a vital role in the initiation of the swallowing reflex and is thought to decline as part of the aging-process. Taste and smell functions appear to decline with age as well. The aim of our study was to generate data of oral sensitivity in healthy participants for future studies and to analyse age-related changes and their interdependence by measuring oral sensitivity, taste, and smell function. The experiment involved 30 participants younger than and 30 participants older than 60. Sensitivity threshold as a surrogate of oral sensitivity was measured at the anterior faucial pillar by electrical stimulation using commercially available pudendal electrode mounted on a gloved finger. Smell and taste were evaluated using commercially available test kits. Mean sensitivity was lower in young participants compared to older participants (1.9 ± 0.59 mA vs. 2.42 ± 1.03 mA; p = 0.021). Young participants also performed better in smell (Score 11.13 ± 0.86 vs 9.3 ± 1.93; p < 0.001) and taste examinations (Score 11.83 ± 1.86 vs 8.53 ± 3.18; p < 0.001). ANCOVA revealed a statistical association between sensitivity and smell (p = 0.08) that was moderated by age (p = 0.044). Electrical threshold testing at the anterior faucial pillar is a simple, safe, and accurate diagnostic measure of oral sensitivity. We detected a decline of oral sensitivity, taste, and smell in older adults.Trial registration: Clinicaltrials.gov, NCT03240965. Registered 7th August 2017- https://clinicaltrials.gov/ct2/show/NCT03240965 .

Improved Balance and Gait Ability and Basic Activities of Daily Living after Comprehensive Geriatric Care in Frail Older Patients with Fractures.

(1) Purpose: Comprehensive geriatric care (CGC) is a multidisciplinary treatment approach for elderly patients. We aimed to investigate outcomes in fracture patients who had been treated using this approach in a large geriatric unit. (2) Methods: This observational cohort study assessed the gait function (using the Tinetti Balance and Gait Test (TBGT)) and basic activities of daily living (ADL) (using the Barthel index (BI)) before and after CGC and compared the results. Baseline data, walking ability assessments (Timed Up and Go, TUG), and cognitive status (mini mental status examination, MMSE) were also analyzed in the subgroup of patients with versus without fractures. (3) Results: Out of 1263 hospitalized patients, 1099 received CGC (median age: 83.1 years (IQR: 79.0-87.8 years); 64.1% were female). TBGT improvement was observed in 90.7% and BI increased in 82.7% of fracture patients. A TBGT improvement of >5 was noted in 47.3% and was associated with female sex, a lower BI at admission (median: 40 versus 45; p = 0.010), and poorer mobility on admission (TUG: median 5 versus 4; p = 0.001). An improvement in BI of ≥15 was observed in 63.0% of the cases, and was associated with a better cognitive status (MMSE: median 25 versus 18; p = 0.001) and inversely associated with diabetes mellitus and a previous stroke. (4) Conclusion: CGC in specialized geriatric units improves the balance and gait and the basic ADL in geriatric patients. After fracture, female patients are more likely to experience improvements in gait and balance, while patients with better cognitive condition are more likely to experience improvements in ADL.

Facilitation of oral sensitivity by electrical stimulation of the faucial pillars.

Dysphagia is common in neurological disease. However, our understanding of swallowing and its central nervous control is limited. Sensory information plays a vital role in the initiation of the swallowing reflex and is often reduced in stroke patients. We hypothesized that the sensitivity threshold of the anterior faucial pillar could be facilitated by either electrical stimulation (ES) or taste and smell information. The sensitivity threshold was measured by ES in the anterior faucial pillar region. The measurement was repeated 5 min after baseline. Thirty minutes after baseline, the participants underwent a test for taste and smell. Immediately after the test, the ES was repeated. Thirty healthy volunteers with a mean age of 27 ± 5.1 participated in the trial. Mean sensitivity threshold at baseline was 1.9 ± 0.59 mA. The values 5 min after baseline (1.74 ± 0.56 mA, p = 0.027) and 30 min after baseline (1.67 ± 0.58 mA, p = 0.011) were significantly lower compared to the baseline, but there was no difference between the latter (p = 0.321). After 5 min, a potentially facilitating effect was found on oral sensitivity by ES of the faucial pillar area. Thirty minutes later, this effect was still present.Trial registration Clinicaltrials.gov, NCT03240965. Registered 7th August 2017- https://clinicaltrials.gov/ct2/show/NCT03240965 .

Flexible endoscopic evaluation of swallowing (FEES) to determine neurological intensive care patients' oral diet.

PURPOSE: Dysphagia is common in critically ill neurological patients and is associated with a high mortality and morbidity. Data on the usefulness of flexible endoscopic examination of swallowing (FEES) in neurological intensive care unit (ICU) patients are lacking, raising the need for evaluation. METHOD: FEES was performed in neurological intensive care patients suspected of dysphagia. We correlated findings with baseline data, disability status, pneumonia and duration of hospitalisation, as well as a need for mechanical ventilation or tracheotomy. RESULT: This analysis consisted of 125 patients with suspected dysphagia. Most of the patients (81; 64,8%) suffered from acute stroke. Dysphagia was diagnosed using FEES in 90 patients (72%). FEES results led to dietary modifications in 80 patients (64%). The outcome at discharge was worse in dysphagic stroke patients diagnosed by FEES as compared to non-dysphagic stroke patients (p = 0.009). Patients without oral diet had higher need for intubation (p = 0.007), tracheotomy (p = 0.032) and higher mortality (p < 0.001) in comparison to patients with at least small amounts of oral intake. CONCLUSION: As the clinical assessment of the patients often classified the dysphagia incorrectly, the broad use of FEES in ICU patients might help to adequately adjust patients' oral diet. This knowledge might contribute to lower mortality and morbidity.

Transcranial sonography for diagnosis of Parkinson's disease.

BACKGROUND: In idiopathic Parkinson's disease (IPD) transcranial sonography (TCS) represents an alternative diagnostic method to verify clinical diagnosis. Although the phenomenon of an increased echogenicity of the Substantia nigra (SN) is well known this method is still not widly used in the diagnostic workup. Until now reliability of this method is still a matter of debate, partly because data only existed from a few laboratories using the same ultrasound machine. Therefore our study was conducted to test the reliability of this method by using a different ultrasound device and examining a large population of control and IPD subjects by two examiners to calculate interobserver reliability. METHOD: In this study echogenicity of SN was examined in 199 IPD patients and 201 control subjects. All individuals underwent a neurological assessment including Perdue pegboard test and Webster gait test. Using a Sonos 5500 ultrasound device area of SN was measured, echogenicity of raphe, red nuclei, thalamus, caudate and lenticular nuclei, width of third and lateral ventricle were documented. RESULTS: We found a highly characteristic enlargement of the SN echogenic signal in IPD. The cut-off value for the SN area was established using a ROC curve with a sensitivity of 95% corresponding to an area of SN of 0.2 cm2 and was found to be equivalent to the cut-off values of other studies using different ultrasound devices. CONCLUSIONS: Our study shows that TCS is a reliable and highly sensitive tool for differentiation of IPD patients from individuals without CNS disorders.

Botulinum toxin improves reduced dorsiflexion after Achilles tendon surgery.

Generally, outcome after surgical repair of complete Achilles tendon rupture is good. However, some patients have ongoing problems with dorsiflexion of the ankle joint. We report on eight patients, who did not achieve heel contact because of reduced ankle dorsiflexion 5 months after surgical repair of complete Achilles tendon rupture. All patients received at least three cycles of injections with 200-300 units of Botulinum toxin A (BOTOX) into the gastrocnemius and soleus muscle. Weakening of the triceps surae by Botulinum toxin allowed patients to perform the required exercises and to tolerate casting at night. Thus, all patients were able to tolerate plantigrade foot position 9 months after beginning of Botulinum toxin treatment. At final follow-up after 2 years, pain had significantly improved, and a mean dorsiflexion of 21 degrees was reached. In conclusion, treatment of the calf muscles with BOTOX is a safe and effective method to improve restricted dorsiflexion in patients after Achilles tendon repair.

Torticollis under cyclobenzaprine.

The muscle-relaxing 5-HT(2) receptor antagonist cyclobenzaprine is structurally closely related to amitriptyline. It is widely used to treat patients presenting with back pain and fibromyalgia. Very rarely cyclobenzaprine toxicity can result in extrapyramidal symptoms, but occurrence of torticollis has not been reported so far. We report on a patient presenting with torticollis and myoclonic movements after treatment with cyclobenzaprine, who was successfully treated with intravenous biperiden. This case might be additional evidence for the necessity of appropriate dosage in case of liver impairment. Secondly there are possibly consequences as regards the therapy of motor side effects.

Reduced central sympathetic activity in Parkinson's disease.

OBJECTIVE: With a combination of different sympathetic tests, we aimed to elucidate whether impairment of sympathetic function in Parkinson's disease (PD) is the consequence of a central or peripheral efferent dysfunction. METHODS: Thirty-five patients with early-to-intermediate PD (median age: 63 years; IQR: 57-67 years; disease duration 1-9 years, 15 women) and 20 age- and sex-matched healthy controls (median age: 64.5 years; IQR: 58-68 years; 10 women) were recruited. Autonomic testing was performed in two subgroups and included the assessment of resting cardiovascular parameters, postprandial hypotension (PPH), orthostatic hypotension (OH), and vasoconstriction induced by intradermal microdialysis with different concentrations of norepinephrine (NE; 10-5 ; 10-6 ; 10-7 ; 10-8 ) and by cold through forehead cooling. We also used sympathetic multiunit microneurography (muscle sympathetic nerve activity; MSNA; burst frequency (BF): bursts per minute; burst incidence (BI): bursts per 100 heart beats) and evaluated the presence of phosphorylated α-synuclein deposits in skin innervation in biopsies from the thighs by immunohistohemistry. RESULTS: Diastolic blood pressure was higher in the PD group at rest (p < .001) and during OH (F = 6.533; p = .022). Vasoconstriction induced by NE microdialysis and cold was unchanged in PD patients. MSNA was lower in PD patients than in controls (BF: p = .001; BI: p = .025). Phosphorylated α-synuclein deposits could be found only in PD patients. CONCLUSION: We did not find indications for peripheral sympathetic nerve fiber dysfunction or adrenoreceptor sensitivity changes. The decreased MSNA argues in favor of central sympathetic impairment.

One decade of oral anticoagulation in stroke patients: Results from a large country-wide hospital-based registry.

Background New evidence regarding stroke prevention in atrial fibrillation has been published. Implementing knowledge into clinical practice remains challenging. Aims To investigate oral anticoagulants in stroke patients documented in a nationwide registry. Methods The database is an obligatory federal-state-wide hospital-based registry that covers more than 95% of all ischemic strokes, transient ischemic attacks and intracerebral hemorrhages in a community of more than six million inhabitants (Hesse/Germany). We analyzed oral anticoagulants prescribed on discharge in patients with stroke or transient ischemic attack during 2006-2015. Results From 2006 to 2015, we annually selected median 20,895 patients. From 2006 to 2015, the proportion of patients treated with oral anticoagulants increased (9.8% to 24%). The annual proportion of patients with atrial fibrillation remained constant (median: 23%). In atrial fibrillation patients treated with oral anticoagulants, the age increased (median 2008/2009: 76.9 years vs. 2014/2015 79.4 years). The percentage of treated individuals in atrial fibrillation increased dramatically (2006: 30.1% to 2015: 74.5%); in 2015, 30.8% of these patients received vitamin K antagonists and 70.2% new oral anticoagulants. Independent factors associated with new oral anticoagulants therapy were a previous medication with new oral anticoagulants and a treatment on stroke unit. Between new oral anticoagulants- and vitamin K antagonists-treated patients (2015), no differences in age were noted (both mean: 79.4 years). Conclusions The new oral anticoagulants availability enhanced a general trend treating more target patients with oral anticoagulants.

What is the value of fibre-endoscopic evaluation of swallowing (FEES) in neurological patients? A cross-sectional hospital-based registry study.

OBJECTIVES: Fibre-endoscopic evaluation of swallowing (FEES) to detect dysphagia is gaining more and more importance as a diagnostic tool. Therefore, we have investigated the impact of FEES in neurological patients in a clinical setting. DESIGN: Cross-sectional hospital-based registry. SETTING: Primary acute care in a neurological department of a German university hospital. PARTICIPANTS: 241patients with various neurological diseases who underwent FEES procedure. PRIMARY AND SECONDARY OUTCOME MEASURES: Dysphagia and related comorbidities. RESULTS: 267 FEES were performed in 241 patients with various neurological diagnoses. Dysphagia was diagnosed in 68.9% of the patients. In only 33.1% of the patients, appropriate oral diet was chosen prior to FEES. A relevant dysphagia occurred more often in patients with structural brain lesions (83.1% vs 65.3%, P=0.001), patients with dysphagia had a longer hospitalisation (median 18 (IQR 12-30) vs 15 days (IQR 9.75-22.75), P=0.005) and had a higher mortality (8.4% vs 1.3%, P=0.041). When the oral diet was changed, we observed a lower pneumonia rate (36% vs 50%, P=0.051) and a lower mortality (3.7% vs 11.3%, P=0.043) in comparison to no change of oral diet. A restriction of oral diet was identified more often in older patients (median 75 years (IQR 66.3-82 years) vs median 72 years (IQR 60-79 years), P=0.01) and in patients with structural brain lesions (86.8% vs 73.1%, P=0.05). CONCLUSION: On clinical investigation, dysphagia was misjudged for the majority of the patients. FEES might help to compensate this drawback, revising the diet regime in nearly 70% of the patients.

Making stem cell lines suitable for transplantation.

Human stem cells, progenitor cells, and cell lines have been derived from embryonic, fetal, and adult sources in the search for graft tissue suitable for the treatment of CNS disorders. An increasing number of experimental studies have shown that grafts from several sources survive, differentiate into distinct cell types, and exert positive functional effects in experimental animal models, but little attention has been given to developing cells under conditions of good manufacturing practice (GMP) that can be scaled up for mass treatment. The capacity for continued division of stem cells in culture offers the opportunity to expand their production to meet the widespread clinical demands posed by neurodegenerative diseases. However, maintaining stem cell division in culture long term, while ensuring differentiation after transplantation, requires genetic and/ or oncogenetic manipulations, which may affect the genetic stability and in vivo survival of cells. This review outlines the stages, selection criteria, problems, and ultimately the successes arising in the development of conditionally immortal clinical grade stem cell lines, which divide in vitro, differentiate in vivo, and exert positive functional effects. These processes are specifically exemplified by the murine MHP36 cell line, conditionally immortalized by a temperature-sensitive mutant of the SV40 large T antigen, and cell lines transfected with the c-myc protein fused with a mutated estrogen receptor (c-mycERTAM), regulated by a tamoxifen metabolite, but the issues raised are common to all routes for the development of effective clinical grade cells.

Patient Registry of Spasticity Care World: Data Analysis Based on Physician Experience.

OBJECTIVE: The aim of the study was to report physician experience-based "real-world" treatment patterns with botulinum toxin type A in patients with stroke and traumatic brain injury. DESIGN: A prospective, multicenter, international observational registry design was used. RESULTS: Six hundred twenty-seven participants with stroke and 132 participants with traumatic brain injury were assessed and treated by 17 more experienced physicians and 12 less experienced physicians. Due to the limited usage of abobotulinumtoxinA Dysport and incobotulinumtoxinA Xeomin, data were reported on onabotulinumtoxinA BOTOX only. Based on physician experience, onabotulinumtoxinA doses were statistically different with larger mean doses injected by more experienced physicians in the upper limb (59.9 [39.0], P = 0.001) and in the lower limb (101.8 [69.2], P < 0.001). Treated deformities significantly differed for both upper limb and lower limb (P < 0.001). More experienced physicians showed a larger mean change in Ashworth Scale scores from baseline for the equinovarus/equinus foot and stiff knee (P = 0.001 and 0.03). Less experienced physicians showed a larger mean change in Ashworth Scale scores from baseline for the adducted thigh (P = 0.05). Less experienced physicians had statistically significant larger change in hand pain scores for clenched fist deformity treatment at follow-up compared with more experienced physicians (P = 0.01). Physician experience demonstrated a significant difference on patients reported satisfaction toward their secondary goal with higher scores for more experienced physician (P = 0.04). CONCLUSIONS: This international registry provides clinical nuances of treatment based on physician clinical experience in a robust sample size.

Nigrosome 1 visibility at susceptibility weighted 7T MRI-A dependable diagnostic marker for Parkinson's disease or merely an inconsistent, age-dependent imaging finding?

BACKGROUND: Visualisation of nigrosome 1, a substructure of the healthy substantia nigra, was restricted in susceptibility weighted MR imaging in almost all patients with Parkinson's disease studied so far. The purpose of this study was to determine the degree of visibility of this substructure in subjects without Parkinson's disease and to examine the potential link between increasing brain iron accumulation with age and its detectability. METHODS: In 46 subjects (21 women, 25 men; 19 to 75 y; mean age: 44.5; SD: 15.6) examined with susceptibility weighted MR imaging at 7T visibility of nigrosome 1 was rated and classified. We assessed differences related to age and to signal intensities in the substantia nigra, red nucleus and putamen as correlates of the individual iron concentration. RESULTS: In 93% nigrosome 1was at least unilaterally clearly present. In 24% at least one-sided limited visibility was observed. Using predefined classification criteria the specificity of the visibility across all age groups reached approximately 94%. We found no correlation with increasing iron concentrations with age. CONCLUSION: Aging with a related increase in iron concentration probably does not affect the visibility of nigrosome 1 at 7T SWI MRI. Our results support the role of this feature as a future differential diagnostic tool but further large-scale prospective studies are needed to better define the extent of a "limited visibility" to which an individual can be considered healthy.

Training of executive functions in Parkinson's disease.

Cognitive disturbances are common in Parkinson's disease (PD). Examination of cognitive function often reveals deficits in executive functions, including maintenance and inhibition of attention, flexibility in thinking, and planning. The involvement of the dopaminergic system in cognitive executive functions has been suggested by numerous studies. The aim of the present study was to analyze the effect of cognitive training on cognitive performance of PD-patients (N=26). Half of the patients participated in a cognitive training regimen, while the other patients only received standard treatment. The outcome showed improved performance of the group with cognitive treatment in two executive tasks after the training period, while no improvement was seen in the standard-treatment group. The results indicate that specific training is required for improvement of executive functions, while general rehabilitation is not sufficient. Thus, PD-patients might benefit from a short-term cognitive executive function training program that is tailored to the individual patient's needs.

Nestin expression is lost in a neural stem cell line through a mechanism involving the proteasome and Notch signalling.

Neural stem cells (NSCs) are believed to repair brain damage primarily through cell replacement: i.e., the ability to regenerate lost neurons and glia in a site-specific fashion. The neural stem cell line, MHP36, has been shown to have this capacity, but we have little idea of the molecular mechanisms that control the differentiation of such cells during brain repair. In this study we show that an early event in the differentiation of MHP36 cells, both in vivo and in vitro, is the loss of expression of the intermediate filament protein, nestin. We use a co-culture assay to show that loss of nestin is fast, being detectable after just 1 h and complete in 4 h, and is controlled by proteasome degradation rather than down-regulation of de novo nestin synthesis. We also show that nestin loss is regulated by Notch, and mediated by cell contact.

The frequency and significance of 'striatal toe' in parkinsonism.

A striatal toe has been defined as an apparent extensor plantar response, without fanning of the toes, in the absence of any other signs suggesting dysfunction of the cortico-spinal tract. Little is known about the frequency and significance of this sign in parkinsonian syndromes. We prospectively examined 62 patients (Parkinson's disease: other akinetic-rigid syndromes=38:24) for the presence or absence of striatal toe and extensor plantar responses, as defined by Babinski. Details of the history, physical findings and investigations previously undertaken were rated and examined for their relevance to the response obtained from the hallux. Of the 62 patients, 17 patients showed an upgoing plantar response, of whom 13 (Parkinson's disease: other akinetic-rigid syndromes=7:6) had striatal toes, either unilateral (10) or bilateral (3). The remaining four patients showed a classical Babinski sign (Parkinson's disease: other akinetic-rigid syndromes=2:2). There was no lateralising relationship between lesions of the basal ganglia found on imaging and the side of the striatal toe, or the side of dyskinesias found at the time of examination. However, there appeared to be a greater frequency of dyskinesias and evidence of lesions involving the basal ganglia on imaging in patients with striatal toes compared with those who showed a plantar response other than upgoing. The possible relevance of these findings is discussed.

Exercise training and Parkinson's disease: placebo or essential treatment?

Exercise training is often recommended for patients who have Parkinson's disease. Until the debate about the pathophysiologic cause of impaired movement in parkinsonism is settled, it is difficult to develop a specific exercise treatment for symptoms that include hypokinesia, tremor, and muscular rigidity. Most of the published studies show a benefit of exercise training, and we provide an overview of the most essential studies and present conclusions for a practical approach to exercise training in parkinsonism.