Enjoy Carefully: The Multifaceted Role of Vitamin E in Neuro-Nutrition.

Vitamin E is often associated with health benefits, such as antioxidant, anti-inflammatory and cholesterol-lowering effects. These properties make its supplementation a suitable therapeutic approach in neurodegenerative disorders, for example, Alzheimer's or Parkinson's disease. However, trials evaluating the effects of vitamin E supplementation are inconsistent. In randomized controlled trials, the observed associations often cannot be substantiated. This could be due to the wide variety of study designs regarding the dosage and duration of vitamin E supplementation. Furthermore, genetic variants can influence vitamin E uptake and/or metabolism, thereby distorting its overall effect. Recent studies also show adverse effects of vitamin E supplementation regarding Alzheimer's disease due to the increased synthesis of amyloid ß. These diverse effects may underline the inhomogeneous outcomes associated with its supplementation and argue for a more thoughtful usage of vitamin E. Specifically, the genetic and nutritional profile should be taken into consideration to identify suitable candidates who will benefit from supplementation. In this review, we will provide an overview of the current knowledge of vitamin E supplementation in neurodegenerative disease and give an outlook on individualized, sustainable neuro-nutrition, with a focus on vitamin E supplementation.

The PhINEST study - Pharyngeal ICU Novel Electrical Stimulation Therapy: Study protocol of a prospective, multi-site, randomized, sham-controlled, single-blind (outcome assessor-blinded) study.

INTRODUCTION: Post-extubation dysphagia is commonly observed in ICU patients and associated with increased aspiration rates, delayed resumption of oral intake/ malnutrition, prolonged ICU and hospital length of stay, decreased quality of life, and increased mortality. Conventional therapeutic approaches are limited. Pharyngeal electrical stimulation (PES) was previously shown to improve swallowing function and airway safety in severely dysphagic tracheostomised stroke patients. METHODS: In a multi-center, single-blind, 1:1 randomized controlled study, up to 400 (360 evaluable) mixed emergency adult ICU patients with recent extubation following mechanical ventilation and confirmed oropharyngeal dysphagia will be enrolled at investigational academic ICUs. Primary objective is to evaluate the effectiveness of PES in reducing the severity of unsafe swallows. Patients will be randomized to receive PES (or sham) treatment on 3 consecutive days in addition to best supportive care. Primary endpoint is a composite of 2 endpoints with hierarchy based on clinical priorities: DISCUSSION:: This study will evaluate the effects of PES on swallowing safety in critically ill ICU patients post mechanical ventilation with oropharyngeal dysphagia.

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.

Pharyngeal Electrical Stimulation for Treatment of Dysphagia in Subacute Stroke: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Dysphagia is common after stroke, associated with increased death and dependency, and treatment options are limited. Pharyngeal electric stimulation (PES) is a novel treatment for poststroke dysphagia that has shown promise in 3 pilot randomized controlled trials. METHODS: We randomly assigned 162 patients with a recent ischemic or hemorrhagic stroke and dysphagia, defined as a penetration aspiration score (PAS) of ≥3 on video fluoroscopy, to PES or sham treatment given on 3 consecutive days. The primary outcome was swallowing safety, assessed using the PAS, at 2 weeks. Secondary outcomes included dysphagia severity, function, quality of life, and serious adverse events at 6 and 12 weeks. RESULTS: In randomized patients, the mean age was 74 years, male 58%, ischemic stroke 89%, and PAS 4.8. The mean treatment current was 14.8 (7.9) mA and duration 9.9 (1.2) minutes per session. On the basis of previous data, 45 patients (58.4%) randomized to PES seemed to receive suboptimal stimulation. The PAS at 2 weeks, adjusted for baseline, did not differ between the randomized groups: PES 3.7 (2.0) versus sham 3.6 (1.9), P=0.60. Similarly, the secondary outcomes did not differ, including clinical swallowing and functional outcome. No serious adverse device-related events occurred. CONCLUSIONS: In patients with subacute stroke and dysphagia, PES was safe but did not improve dysphagia. Undertreatment of patients receiving PES may have contributed to the neutral result. CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN25681641.

Electrical pharyngeal stimulation for dysphagia treatment in tracheotomized stroke patients: a randomized controlled trial.

PURPOSE: Treatment of post-stroke dysphagia is notoriously difficult with different neurostimulation strategies having been employed with a variable degree of success. Recently, electrical pharyngeal stimulation (EPS) has been shown to improve swallowing function and in particular decrease airway aspiration in acute stroke. We performed a randomized controlled trial to assess EPS effectiveness on swallowing function in severely dysphagic tracheotomized patients. METHODS: All consecutive stroke patients successfully weaned from the respirator but with severe dysphagia precluding decannulation were screened for eligibility. Eligible patients were randomized to receive either EPS (N = 20) or sham stimulation (N = 10) over three consecutive days. Primary endpoint was ability to decannulate the patient. Swallowing function was assessed using fiberoptic endoscopy. Patients having received sham stimulation were offered EPS treatment during unblinded follow-up if required. Investigators were blinded to the patient's study group allocation. RESULTS: Both groups were well matched for age, stroke severity, and lesion location. Decannulation after study intervention was possible in 75% of patients of the treatment group and in 20% of patients of the sham group (p < 0.01). Secondary outcome parameters did not differ. No adverse events occurred. CONCLUSION: In this pilot study, EPS enhanced remission of dysphagia as assessed with fiberoptic endoscopic evaluation of swallowing (FEES), thereby enabling decannulation in 75% of patients.

Cervical artery dissection--clinical features, risk factors, therapy and outcome in 126 patients.

The highly variable clinical course of cervical artery dissections still poses a major challenge to the treating physician. This study was conducted (1) to describe the differences in clinical and angiographic presentation of patients with carotid and vertebral artery dissections (CAD, VAD), (2) to define the circumstances that are related to bilateral arterial dissections, and (3) to determine factors that predict a poor outcome. Retrospectively and by standardised interview, we studied 126 patients with cervical artery dissections. Preceding traumata, vascular risk factors, presenting local and ischemic symptoms, and patient-outcome were evaluated. Patients with CAD presented more often with a partial Horner's syndrome and had a higher prevalence of fibromuscular dysplasia than patients with VAD. Patients with VAD complained more often of neck pain, more frequently reported a preceding chiropractic manipulation and had a higher incidence of bilateral dissections than patients with CAD. Bilateral VAD was significantly related to a preceding chiropractic manipulation. Multivariate analysis showed that the variables stroke and arterial occlusion were the only independent factors associated with a poor outcome. This study emphasises the potential dangers of chiropractic manipulation of the cervical spine. Probably owing to the systematic use of forceful neck-rotation to both sides, this treatment was significantly associated with bilateral VAD. Patients with dissection-related cervical artery occlusion had a significantly increased risk of suffering a disabling stroke.