Diagnosing, imaging, and successfully treating a debilitating case of Bing-Neel syndrome: A multidisciplinary feat.

Key Clinical Message: We present a case of Bing-Neel syndrome a rare central nervous system lymphoplasmocytic lymphoma associated with Waldenstrom macroglobulinemia. Diagnosis should be considered in the context of unexplained neurological symptoms in the presence of macroglobulinemia. Abstract: Waldenstroms macroglobulinaemia (WM) is a rare B-cell lymphoma representing ~2% of all hematological malignancies. While most neurological complications of WM are secondary to the overproduction of immunoglobulin M (IgM), Bing-Neel syndrome (BNS) is an extremely rare direct central nervous system (CNS) infiltration by malignant lymphoplasmocytic lymphoma (LPL) cells. Limited information on BNS exists in the literature with sparse case reports and case series. Here, we present a diagnostically challenging BNS case successfully treated with systemic chemoimmunotherapy and ibrutinib, with remarkable clinical response.

Supplementation With Carotenoids, Omega-3 Fatty Acids, and Vitamin E Has a Positive Effect on the Symptoms and Progression of Alzheimer's Disease.

BACKGROUND: Preliminary work by our center has reported behavior and functional benefits in patients with Alzheimer's disease (AD) following targeted micronutritional supplementation. OBJECTIVE: To build on the existing exploratory research and investigate the impact of these micronutrients on the natural progression of AD in a randomized controlled trial. METHODS: Patients with mild-moderate AD consumed daily 1 g fish oil (of which 500 mg DHA, 150 mg EPA), 22 mg carotenoids (10 mg lutein, 10 mg meso-zeaxanthin, 2 mg zeaxanthin), and 15 mg vitamin E or placebo for 12 months in a double-blind, placebo-controlled, randomized clinical trial. Carotenoids, ω-3FAs, and vitamin E were quantified in blood. Carotenoids were also measured in skin. AD severity was measured using the mini-mental state examination and dementia severity rating scale tools. Behavior, mood, and memory were measured using an informant-based questionnaire. RESULTS: Following 12 months of supplementation, the active group (n = 50) compared to the placebo group (n = 27), demonstrated statistically significant improvements in skin carotenoid measurements, blood carotenoids, ω-3FAs, and vitamin E concentrations (p < 0.05, for all). The active group also performed better in objective measures of AD severity (i.e., memory and mood), with a statistically significant difference reported in the clinical collateral for memory (p < 0.001). CONCLUSION: Exponential increases in the prevalence of AD and its relentless progressive nature is driving the need for interventions that help to ameliorate symptoms and improve quality of life in AD patients. Given the positive outcomes demonstrated in this trial, this combined micronutrient dietary supplement should be considered in the overall management of AD.

Quality improvement project to improve patient outcomes by reducing door to CT and door to needle time and increasing appropriate referrals for endovascular thrombectomy.

This paper describes a stroke quality improvement (QI) project in a primary stroke centre in a 431-bed hospital serving a local population of 114 000 people. Approximately 170 acute strokes are treated each year in a seven-bed stroke unit managed by three geriatricians with a subspecialty interest in stroke. 24-hour CT radiology service is available. Endovascular thrombectomy (EVT) is performed by neuro-interventional radiology at one of two comprehensive stroke centres located 90-120 min away.In 2018, as part of a national collaborative QI initiative a new national thrombectomy referral pathway was introduced with an aim that all eligible patients be referred for EVT. This initiative included maximising timely access to CT and thrombolysis. Review of local data highlighted significant deficits in these areas.A local QI team convened and a multidisciplinary approach was employed to map the existing process for CT access and time to thrombolysis decision.We describe how focused timesaving interventions such as; new emergency and radiology department 'pre-alerts', dedicated acute stroke pagers, new 'FAST' registration by clerical staff, new CT ordering codes and new 'FAST packs' (including tissue plasminogen activator, paper National Institute of Health Stroke Scale scoring tools, consent forms and EVT patient selection tools) were created and incorporated into a multidisciplinary detailed clinical stroke care pathway.We describe how we achieved our SMART aims; to reduce our door to CT time and to reduce our door to needle time to the national target of less than 30 min. A third aim was to increase the number of patients referred for EVT from our centre.This project is an accurate description of how a multidisciplinary approach combined with teamwork and effective communication can create sustainable improved patient care and is generalisable to all institutions that require timely referral to external centres for EVT.

Omega-3 fatty acid, carotenoid and vitamin E supplementation improves working memory in older adults: A randomised clinical trial.

BACKGROUND & AIMS: Accumulating evidence suggests that omega-3 fatty acids (ω-3FAs), carotenoids and vitamin E can improve cognitive performance. However, their collective impact on cognition has not yet been investigated in healthy individuals. This study investigated the combined effect of ω-3FA, carotenoid and vitamin E supplementation on the cognitive performance of older adults. METHODS: Cognitively healthy individuals aged ≥65 years consumed daily 1 g fish oil (of which 430 mg docosahexaenoic acid, 90 mg eicosapentaenoic acid), 22 mg carotenoids (10 mg lutein, 10 mg meso-zeaxanthin, 2 mg zeaxanthin) and 15 mg vitamin E or placebo for 24 months in a double-blind, placebo-controlled, randomised clinical trial. RESULTS: Following 24-month supplementation, individuals in the active group (n = 30; aged 69.03 ± 4.41 years; 56.7% female) recorded significantly fewer errors in working memory tasks than individuals receiving placebo (n = 30; aged 69.77 ± 3.74 years; 70% female) (point estimate effect sizes ranged 0.090-0.105). Interestingly, as the cognitive load of the working memory tasks increased, the active group outperformed the placebo group. Statistically significant improvements in tissue carotenoid concentrations, serum xanthophyll carotenoid concentrations and plasma ω-3FA concentrations were also observed in the active group versus placebo (point estimate effect sizes ranged 0.078-0.589). Moreover, the magnitude of change of carotenoid concentrations in tissue, and ω-3FA and carotenoid concentrations in blood were related to the magnitude of change in working memory performance. CONCLUSION: These results support a biologically plausible rationale whereby these nutrients work synergistically, and in a dose-dependent manner, to improve working memory in cognitively healthy older adults. Increasing nutritional intake of carotenoids and ω-3FAs may prove beneficial in reducing cognitive decline and dementia risk in later life. STUDY ID NUMBER: ISRCTN10431469; https://doi.org/10.1186/ISRCTN10431469.

Diet and Exercise for FRAILty (DEFRAIL): protocol for a study to examine the effect of a novel community-based group exercise and nutritional intervention, designed to reverse frailty in older adults.

INTRODUCTION: Frailty refers to a multifaceted age-related loss of physiological reserve. Aside from the immediate challenges it presents, it is also associated with various adverse health outcomes. Given our ageing population, the healthcare and societal costs resulting from frailty present a significant and growing public health challenge. Rapidly accumulating evidence suggests that resistance exercise combined with protein supplementation can reverse frailty in older adults. However, translation of these findings into practice has proven difficult, due to either a lack of clarity regarding the interventions used or the use of interventions not suitable for widespread implementation. There remains an absence of evidence-based programmes suitable for delivery to frail older adults in the community. METHODS AND ANALYSIS: This paper outlines the protocol for a study to examine the effect of a novel programme of exercise and protein supplementation. This intervention has been developed by an expert consensus group, specifically for delivery to frail older adults in a group setting in the community. The study will take the form of a within-subjects non-randomised trial. Participants will be assessed at baseline, then following an 8-week period of regular activity, then following the 8-week intervention. Frailty (according to the Fried Frailty criteria) will be the primary outcome measure, along with a range of secondary outcome measures (including physical performance measures, body mass composition, psychosocial assessments and frailty-related biomarkers). If shown to be feasible to implement and effective at reversing frailty, the Diet and Exercise for FRAILty (DEFRAIL) intervention may facilitate more widespread participation in resistance exercise for frail older adults. ETHICS AND DISSEMINATION: This study received ethical approval from the Research Ethics committees of both the Health Service Executive South-Eastern Area and Waterford Institute of Technology. Its findings will be disseminated through journal publications, conference presentations and other forms of public engagement. TRIAL REGISTRATION NUMBER: ISRCTN46458028; Pre-results.

Targeted Nutritional Intervention for Patients with Mild Cognitive Impairment: The Cognitive impAiRmEnt Study (CARES) Trial 1.

Omega-3 fatty acids (ω-3FAs), carotenoids, and vitamin E are important constituents of a healthy diet. While they are present in brain tissue, studies have shown that these key nutrients are depleted in individuals with mild cognitive impairment (MCI) in comparison to cognitively healthy individuals. Therefore, it is likely that these individuals will benefit from targeted nutritional intervention, given that poor nutrition is one of the many modifiable risk factors for MCI. Evidence to date suggests that these nutritional compounds can work independently to optimize the neurocognitive environment, primarily due to their antioxidant and anti-inflammatory properties. To date, however, no interventional studies have examined the potential synergistic effects of a combination of ω-3FAs, carotenoids and vitamin E on the cognitive function of patients with MCI. Individuals with clinically confirmed MCI consumed an ω-3FA plus carotenoid plus vitamin E formulation or placebo for 12 months. Cognitive performance was determined from tasks that assessed global cognition and episodic memory. Ω-3FAs, carotenoids, and vitamin E were measured in blood. Carotenoid concentrations were also measured in tissue (skin and retina). Individuals consuming the active intervention (n = 6; median [IQR] age 73.5 [69.5-80.5] years; 50% female) exhibited statistically significant improvements (p < 0.05, for all) in tissue carotenoid concentrations, and carotenoid and ω-3FA concentrations in blood. Trends in improvements in episodic memory and global cognition were also observed in this group. In contrast, the placebo group (n = 7; median [IQR] 72 (69.5-75.5) years; 89% female) remained unchanged or worsened for all measurements (p > 0.05). Despite a small sample size, this exploratory study is the first of its kind to identify trends in improved cognitive performance in individuals with MCI following supplementation with ω-3FAs, carotenoids, and vitamin E.

The Role of Nutrition for the Aging Population: Implications for Cognition and Alzheimer's Disease.

Improved life expectancy worldwide has resulted in a significant increase in age-related diseases. Dementia is one of the fastest growing age-related diseases, with 75 million adults globally projected to develop the condition by 2030. Alzheimer's disease (AD) is the most common form of dementia and represents the most significant stage of cognitive decline. With no cure identified to date for AD, focus is being placed on preventative strategies to slow progression, minimize the burden of neurological disease, and promote healthy aging. Accumulating evidence suggests that nutrition (e.g., via fruit, vegetables, fish) is important for optimizing cognition and reducing risk of AD. This review examines the role of nutrition on cognition and AD, with specific emphasis on the Mediterranean diet (MeDi) and key nutritional components of the MeDi, namely xanthophyll carotenoids and omega-3 fatty acids. Given their selective presence in the brain and their ability to attenuate proposed mechanisms involved in AD pathogenesis (namely oxidative damage and inflammation), these nutritional compounds offer potential for optimizing cognition and reducing the risk of AD.

Nutritional Intervention to Prevent Alzheimer's Disease: Potential Benefits of Xanthophyll Carotenoids and Omega-3 Fatty Acids Combined.

BACKGROUND: A growing body of scientific evidence suggests that enrichment of certain nutritional compounds in the brain may reduce the risk of Alzheimer's disease (AD). OBJECTIVE: To investigate the impact of supplemental xanthophyll carotenoids plus omega-3 fatty acids on disease progression in patients with AD. METHODS: Three trial experiments were performed. In Trials 1 and 2 (performed on patients with AD over an 18-month period), 12 patients (AD status at baseline: 4 mild and 8 moderate) were supplemented with a xanthophyll carotenoid only formulation (Formulation 1; lutein:meso-zeaxanthin:zeaxanthin 10:10:2 mg/day) and 13 patients (AD status at baseline: 2 mild, 10 moderate, and 1 severe) were supplemented with a xanthophyll carotenoid and fish oil combination (Formulation 2; lutein:meso-zeaxanthin:zeaxanthin 10:10:2 mg/day plus 1 g/day of fish oil containing 430 mg docohexaenoic acid [DHA] and 90 mg eicopentaenoic acid [EPA]), respectively. In Trial 3, 15 subjects free of AD (the control group) were supplemented for 6 months with Formulation 1. Blood xanthophyll carotenoid response was measured in all trials by HPLC. Omega-3 fatty acids were profiled by direct infusion mass spectrometry. RESULTS: Xanthophyll carotenoid concentration increases were significantly greater for Formulation 2 compared to Formulation 1 (p < 0.05), and progression of AD was less for this group (p = 0.003), with carers reporting functional benefits in memory, sight, and mood. CONCLUSION: This preliminary report suggests positive outcomes for patients with AD who consumed a combination of xanthophyll carotenoids plus fish oil, but further study is required to confirm this important observation.

Supplemental Retinal Carotenoids Enhance Memory in Healthy Individuals with Low Levels of Macular Pigment in A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: There is a biologically plausible rationale whereby the dietary carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ), which are collectively referred to as macular pigment (MP) in the central retina (macula), support the maintenance of cognition via their antioxidant and anti-inflammatory properties. OBJECTIVE: To investigate the impact of supplemental L, Z, and MZ on memory, executive function, and verbal fluency among healthy individuals with low MP levels. METHODS: In this double-blind, placebo-controlled, randomized clinical trial, subjects (n = 91; mean±SD age = 45.42±12.40; % male = 51.6) consumed a daily formulation of 10 mg L, 10 mg MZ, and 2 mg Z (n = 45) or placebo (n = 46) for 12 months. Cognitive domains assessed included verbal and visual learning, immediate and delayed memory, executive function, and verbal fluency. MP and serum carotenoid concentrations of L, Z, and MZ were also measured. RESULTS: Following 12-month supplementation, individuals in the active group exhibited statistically significant improvements in memory when compared to the placebo group (paired associated learning [PAL] memory score [rANOVA, p = 0.009]; PAL errors [rANOVA, p = 0.017]). Furthermore, the observed reduction in the number of errors made in the PAL task among those in the intervention group was positively and significantly related to observed increases in MP volume (p = 0.005) and observed increases in serum concentrations of L (p = 0.009). CONCLUSION: This randomized, double-blind, placebo-controlled clinical trial demonstrates a memory-enhancing effect of daily supplementation with L, Z, and MZ in healthy subjects with low MP at baseline. The implications of these findings for intellectual performance throughout life, and for risk of cognitive decline in later life, warrant further study.

A comparison of service organisation and guideline compliance between two adjacent European health services.

INTRODUCTION: Outcomes in stroke patients are improved by a co-ordinated organisation of stroke services and provision of evidence-based care. We studied the organisation of care and application of guidelines in two neighbouring health care systems with similar characteristics. METHODS: Organisational elements of the 2015 National Stroke Audit (NSA) from the Republic of Ireland (ROI) were compared with the Sentinel Stroke National Audit Programme (SSNAP) in Northern Ireland (NI) and the United Kingdom (UK). Compliance was compared with UK and European guidelines. RESULTS: Twenty-one of 28 ROI hospitals (78%) reported having a stroke unit (SU) compared with all 10 in NI. Average SU size was smaller in ROI (6 beds vs. 15 beds) and bed availability per head of population was lower (1:30,633 vs. 1:12,037 p < 0.0001 Chi Sq). Fifty-four percent of ROI patients were admitted to SU care compared with 96% of UK patients (p < 0.0001). Twenty-four-hour physiological monitoring was available in 54% of ROI SUs compared to 91% of UK units (p < 0.0001). There was no significant difference between ROI and NI in access to senior specialist physicians or nurses or in SU nurse staffing (3.9/10 beds weekday mornings) but there was a higher proportion of trained nurses in ROI units (2.9/10 beds vs. 2.3/10 beds (p = 0.02 Chi Sq). CONCLUSION: Whilst the majority of hospitals in both jurisdictions met key criteria for organised stroke care the small size and underdevelopment of the ROI units meant a substantial proportion of patients were unable to access this specialised care.

Clarithromycin Culprit of Benign Intracranial Hypertension.

Benign intracranial hypertension is characterized with increase in CSF opening pressure with no specific etiology. It is predominantly found in women of child bearing age and particularly in individuals with obesity. Visual disturbances or loss and associated headaches are common and can lead to blindness if left untreated. Diagnosis can be achieved once other causes of visual loss, headaches and high opening pressures are excluded. Management consists of serial optic disc assessments although no specific treatment is available despite recent trials using carbonic anhydrase inhibitors. Diet modification and weight management can help in therapy.

Cognitive Function and Its Relationship with Macular Pigment Optical Density and Serum Concentrations of its Constituent Carotenoids.

BACKGROUND: Macular pigment (MP) levels correlate with brain concentrations of lutein (L) and zeaxanthin (Z), and have also been shown to correlate with cognitive performance in the young and elderly. OBJECTIVE: To investigate the relationship between MP, serum concentrations of L and Z, and cognitive function in subjects free of retinal disease with low MP (Group 1, n = 105) and in subjects with AMD (Group 2, n = 121). METHODS: MP was measured using customized heterochromatic flicker photometry and dual-wavelength autofluorescence; cognitive function was assessed using a battery of validated cognition tests; serum L and Z concentrations were determined by HPLC. RESULTS: Significant correlations were evident between MP and various measures of cognitive function in both groups (r = -0.273 to 0.261, p≤0.05, for all). Both serum L and Z concentrations correlated significantly (r = 0.187, p≤0.05 and r = 0.197, p≤0.05, respectively) with semantic (animal) fluency cognitive scores in Group 2 (the AMD study group), while serum L concentrations also correlated significantly with Verbal Recognition Memory learning slope scores in the AMD study group (r = 0.200, p = 0.031). Most of the correlations with MP, but not serum L or Z, remained significant after controlling for age, gender, diet, and education level. CONCLUSION: MP offers potential as a non-invasive clinical biomarker of cognitive health, and appears more successful in this role than serum concentrations of L or Z.

The impact of supplemental macular carotenoids in Alzheimer's disease: a randomized clinical trial.

BACKGROUND: Patients with Alzheimer's disease (AD) exhibit significantly less macular pigment (MP) and poorer vision when compared to control subjects. OBJECTIVE: To investigate supplementation with the macular carotenoids on MP, vision, and cognitive function in patients with AD versus controls. METHODS: A randomized, double-blind clinical trial with placebo and active arms. 31 AD patients and 31 age-similar control subjects were supplemented for six months with either Macushield (10 mg meso-zeaxanthin [MZ]; 10 mg lutein [L]; 2 mg zeaxanthin [Z]) or placebo (sunflower oil). MP was measured using dual-wavelength autofluorescence (Heidelberg Spectralis®). Serum L, Z, and MZ were quantified by high performance liquid chromatography. Visual function was assessed by best corrected visual acuity and contrast sensitivity (CS). Cognitive function was assessed using a battery of cognition tests, including the Cambridge Neuropsychological Test Automated Battery (CANTAB)). RESULTS: Subjects on the active supplement (for both AD and non-AD controls) exhibited statistically significant improvement in serum concentrations of L, Z, MZ, and MP (p < 0.001, for all) and also CS at (p = 0.039). Also, for subjects on the active supplement, paired samples t-tests exhibited four significant results (from five spatial frequencies tested) in the AD group, and two for the non-AD group, and all indicating improvements in CS. We found no significant changes in any of the cognitive function outcome variables measured (p > 0.05, for all). CONCLUSION: Supplementation with the macular carotenoids (MZ, Z, and L) benefits patients with AD, in terms of clinically meaningful improvements in visual function and in terms of MP augmentation.

Macular pigment, visual function, and macular disease among subjects with Alzheimer's disease: an exploratory study.

BACKGROUND: The macula (central retina) contains a yellow pigment, comprising the dietary carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin, known as macular pigment (MP). The concentrations of MP's constituent carotenoids in retina and brain tissue correlate, and there is a biologically-plausible rationale, supported by emerging evidence, that MP's constituent carotenoids are also important for cognitive function. OBJECTIVE: To investigate if patients with Alzheimer's disease (AD) are comparable to controls in terms of MP and visual function. METHODS: 36 patients with moderate AD and 33 controls with the same age range participated. MP was measured using dual-wavelength autofluorescence (Heidelberg Spectralis®); cognitive function was assessed using a battery of cognition tests (including Cambridge Neuropsychological Test Automated Battery). Visual function was recorded by measuring best corrected visual acuity (BCVA) and contrast sensitivity (CS). Serum L and Z concentrations (by HPLC) and age-related macular degeneration (AMD, by retinal examination) status were also assessed. RESULTS: In the AD group, central MP (i.e., at 0.23°) and MP volume were significantly lower than the control group (p < 0.001 for both), as were measures of BCVA, CS, and serum L and Z concentrations (p < 0.05, for all). CONCLUSION: AD patients were observed to exhibit significantly less MP, lower serum concentrations of L and Z, poorer vision, and a higher occurrence of AMD when compared to control subjects. A clinical trial in AD patients designed to investigate the impact of macular carotenoid supplementation with respect to MP, visual function, and cognitive function is merited.

Circadian and orthostatic blood pressure is abnormal in the carotid sinus syndrome.

The authors' objective was to determine circadian blood pressure behavior and the prevalence of orthostatic hypotension in patients with cardioinhibitory carotid sinus syndrome. A prospective consecutive series of 160 patients (mean age, 72 [65-83]) with recurrent syncope attributed to cardioinhibitory carotid sinus syndrome was recruited. Mean maximal slowing of heart rate was 4.5 seconds (3.0-5.5 seconds) during carotid sinus massage. Patients had cardiovascular assessments, including 24-hour ambulatory blood pressure measurements (recordings every half-hour during daytime, hourly at night) and morning orthostatic blood pressures before pacemaker implants. Ambulatory measurements were compared with those of 98 age- and sex-matched controls. Nocturnal systolic blood pressure (130.0+/-21.0 vs. 122.1+/-16.7 mm Hg; p<0.005), diastolic blood pressure (72.8+/-12.5 vs. 68.7+/-9.7 mm Hg; p<0.005), and heart rate (66.5+/-9.4 vs. 65.2+/-9.7 bpm; p<0.005), were significantly higher in patients and independent of cardiovascular medication, cardiovascular diagnoses, and orthostatic hypotension. Almost one half of carotid sinus syndrome patients also had orthostatic hypotension. Blood pressure behavior is abnormal in patients with carotid sinus syndrome as represented by altered nocturnal blood pressures and high prevalence of orthostatic hypotension.