Anaesthesia associates' clinical activity, case mix, supervision and involvement in peri-operative cardiac arrest: analysis from the 7th National Audit Project.

BACKGROUND: We analysed the clinical practice of anaesthesia associates in the UK, as reported to the 7th National Audit Project of the Royal College of Anaesthetists, and compared these with medically qualified anaesthetists. METHODS: We included data from our baseline survey, activity survey and case registry as with other reports from the project. RESULTS: Among 197 departments of anaesthesia, 52 (26%) employed anaesthesia associates. Of 10,009 responding anaesthesia care providers, 71 (< 1%) were anaesthesia associates, of whom 33 (47%) reporting working nights or weekends (compared with 97% of medically qualified anaesthetists in training and > 90% of consultants). Anaesthesia associates reported less training and confidence in managing peri-operative cardiac arrest and its aftermath compared with medically qualified anaesthetists. Anaesthesia associates were less directly involved in the management and the aftermath of peri-operative cardiac arrest than medically qualified anaesthetists, and the psychological impacts on professional and personal life appeared to be less. Among 24,172 cases, anaesthesia associates attended 432 (2%) and were the senior anaesthesia care provider in 63 (< 1%), with indirect supervision in 27 (43%). Anaesthesia associates worked predominantly in a small number of surgical specialties during weekdays and working daytime hours. Complication rates were low in cases managed by anaesthesia associates, likely reflecting case mix. However, activity and registry case mix data show anaesthesia associates do manage high-risk cases (patients who are older, comorbid, obese and frail) with the potential for serious complications. Registry cases included higher risk cases with respect to the clinical setting and patient factors. CONCLUSION: Anaesthesia associates work in enhanced roles, relative to the scope of practice at qualification agreed by organisations. Recent changes mean the Royal College of Anaesthetists and Association of Anaesthetists do not currently support an enhanced scope of practice.

Advanced life support interventions during intra-operative cardiac arrest among adults as reported to the 7th National Audit Project of the Royal College of Anaesthetists.

BACKGROUND: Few existing resuscitation guidelines include specific reference to intra-operative cardiac arrest, but its optimal treatment is likely to require some adaptation of standard protocols. METHODS: We analysed data from the 7th National Audit Project of the Royal College of Anaesthetists to determine the incidence and outcome from intra-operative cardiac arrest and to summarise the advanced life support interventions reported as being used by anaesthetists. RESULTS: In the baseline survey, > 50% of anaesthetists responded that they would start chest compressions when the non-invasive systolic pressure was < 40-50 mmHg. Of the 881 registry patients, 548 were adult patients (aged > 18 years) having non-obstetric procedures under the care of an anaesthetist, and who had arrested during anaesthesia (from induction to emergence). Sustained return of spontaneous circulation was achieved in 425 (78%) patients and 338 (62%) were alive at the time of reporting. In the 365 patients with pulseless electrical activity or bradycardia, adrenaline was given as a 1 mg bolus in 237 (65%). A precordial thump was used in 14 (3%) patients, and although this was associated with return of spontaneous circulation at the next rhythm check in almost three-quarters of patients, in only one of these was the initial rhythm shockable. Calcium (gluconate or chloride) and 8.4% sodium bicarbonate were given to 51 (9%) and 25 (5%) patients, but there were specific indications for these treatments in less than half of the patients. A thrombolytic drug was given to 5 (1%) patients, and extracorporeal cardiopulmonary resuscitation was used in 9 (2%) of which eight occurred during cardiac procedures. CONCLUSIONS: The specific characteristics of intra-operative cardiac arrest imply that its optimal treatment requires modifications to standard advanced life support guidelines.

Does melatonin administration reduce the incidence of postoperative delirium in adults? Systematic review and meta-analysis.

Postoperative delirium (POD) is common. It is associated with increased morbidity and mortality. Many cases may be preventable and melatonin offers promise as a preventative agent. OBJECTIVE: This systematic review provides an up-to-date synthesis of the evidence on the effect of melatonin in preventing POD. DESIGN: A systematic search of randomised controlled trials of melatonin in POD was run across multiple databases (EMBASE, MEDLINE, CINAHL, PsycINFO) and a clinical trials registry (ClinicalTrials.org) (1 January 1990 to 5 April 2022). Studies examining the effects of melatonin on POD incidence in adults are included. Risk of bias was assessed using the Cochrane risk of bias 2 tool. OUTCOME MEASURES: The primary outcome is POD incidence. Secondary outcomes are POD duration and length of hospital stay. Data synthesis was undertaken using a random-effects meta-analysis and presented using forest plots. A summary of methodology and outcome measures in included studies is also presented. RESULTS: Eleven studies, with 1244 patients from a range of surgical specialties were included. Seven studies used melatonin, in variable doses, and four used ramelteon. Eight different diagnostic tools were used to diagnose POD. Time points for assessment also varied. Six studies were assessed as low risk of bias and five as some concern. The combined OR of developing POD in the melatonin groups versus control was 0.41 (95% CI 0.21 to 0.80, p=0.01). CONCLUSION: This review found that melatonin may reduce the incidence of POD in adults undergoing surgery. However, included studies displayed inconsistency in their methodology and outcome reporting. Further work to determine the optimum regime for melatonin administration, along with consensus of how best to evaluate results, would be beneficial. PROSPERO REGISTRATION NUMBER: CRD42021285019.

Melatonin for the prevention of postoperative delirium in older adults: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Postoperative delirium (POD) is a major cause of morbidity, particularly in elderly patients. Melatonin has been suggested as a low-risk pharmacological intervention to help prevent POD. A previous systematic review found limited high-quality evidence to support the use of melatonin in the prevention of POD. Several further randomised studies have since been published. This systematic review aims to synthesise the evidence from randomised controlled trials (RCTs) examining the effect of melatonin on the prevention of POD in older adults. METHODS AND ANALYSIS: A systematic search of RCTs of melatonin (any dose and formulation) in POD will be run across Embase, Medline, CINAHL and PsychInfo. RCTs published from January 1990 until the end of February 2022 and reporting outcomes for melatonin use to prevent POD in patients will be included. Screening of search results and data extraction from included articles will be performed by two independent reviewers. The primary outcome will be incidence of POD in older adults undergoing surgery. Secondary outcomes are delirium duration and length of hospital stay. The review will also describe the dosage, timing and administration regimes of melatonin therapy and as well as the scales and definitions used to describe POD. A registry review of ongoing trials will be also be performed. For the meta-analysis, data will be pooled using a random effects model to generate a forest plot and obtain an odds ratio (OR) for the incidence of POD. Results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. ETHICS AND DISSEMINATION: No ethical approval is required. This review will be disseminated via peer-reviewed manuscript and conferences. The results will be used as the basis of work to optimise this intervention for future trials in surgical populations. PROSPERO REGISTRATION NUMBER: This review is registered with PROSPERO (CRD42021285019).

Investigating target refraction advice provided to cataract surgery patients by UK optometrists and ophthalmologists.

PURPOSE: To determine whether UK optometrists and ophthalmologists provide target refraction advice to patients prior to cataract surgery, and when this should first be discussed. METHODS: Optometrists and ophthalmologists were asked to complete a survey of two clinical vignettes (both older patients with cataract; a pre-operative myope who routinely read without glasses and a patient using a monovision approach), plus multiple choice and short answer questions either using hard copy or online. RESULTS: Responses were obtained from 437 optometrists and 50 ophthalmologists. Optometrists who reported they would provide target refraction advice were more experienced (median 22 years) than those who would leave this to the Hospital Eye Service (median 10 years). The former group reported it was in the patients' best interest to make an informed decision as they had seen many myopic patients who read uncorrected pre-operatively, and were unhappy that they could no longer do so after surgery. Inexperienced optometrists reported that they did not want to overstep their authority and left the decision to the ophthalmologist. The ophthalmologists estimated their percentage of emmetropic target refractions over the last year to have been 90%. CONCLUSION: Currently, some long-term myopes become dissatisfied after cataract surgery due to an emmetropic target refraction that leaves them unable to read without glasses as they did prior to surgery. Although experienced optometrists are aware of this and attempt to discuss this issue with patients, less experienced optometrists tend not to. This suggests that target refraction needs greater exposure in university training and continuing professional development. To provide patients with the knowledge to make informed decisions regarding their surgery, we suggest an agreed protocol within funded direct referral schemes of initial target refraction discussions by optometrists to introduce the idea of refractive outcomes and outline options, with further discussion with the ophthalmologist to clarify understanding.

Tear Film Surface Quality in Modern Daily Disposable Contact Lens Wear.

OBJECTIVES: As reported previously, tear film surface quality (TFSQ) should be considered in contact lens (CL) fitting. This study followed noninvasive keratograph tear film break-up time (NIKBUT) in CL wearers for 12 months to validate its clinical utility in predicting CL performance. METHODS: Fifty-five subjects (M/F=17/38) aged 26±4 years were prescribed silicone hydrogel or hydrogel CLs. The study included baseline measurements without CLs; 2 visits for CL fitting and control; follow-up after 3, 6, and 12 months of CL wear; and postwear visit without CLs. Ocular Surface Disease Index (OSDI), 8-Item Contact Lens Dry Eye Questionnaire (CLDEQ-8), first and mean NIKBUT (F/M-NIKBUT), fluorescein tear film break-up time (FBUT), and ocular surface staining were evaluated. RESULTS: Post hoc analysis of each pair of visits showed differences between baseline and all CL visits for F-NIKBUT, M-NIKBUT, FBUT, and corneal staining. No difference was reported in symptoms. In addition, differences between baseline and postwear visits were noted in OSDI, M-NIKBUT, FBUT, and corneal staining, with three of the latter parameters showing a downward trend. CONCLUSIONS: No changes in TFSQ and symptoms were reported over 12 months. Introducing NIKBUT as part of routine CL fitting is advised to improve CL fit and predict success.

Biogeochemical processes create distinct isotopic fingerprints to track floodplain rearing of juvenile salmon.

Floodplains represent critical nursery habitats for a variety of fish species due to their highly productive food webs, yet few tools exist to quantify the extent to which these habitats contribute to ecosystem-level production. Here we conducted a large-scale field experiment to characterize differences in food web composition and stable isotopes (δ¹³C, δ¹5N, δ³4S) for salmon rearing on a large floodplain and adjacent river in the Central Valley, California, USA. The study covered variable hydrologic conditions including flooding (1999, 2017), average (2016), and drought (2012-2015). In addition, we determined incorporation rates and tissue fractionation between prey and muscle from fish held in enclosed locations (experimental fields, cages) at weekly intervals. Finally, we measured δ³4S in otoliths to test if these archival biominerals could be used to reconstruct floodplain use. Floodplain-reared salmon had a different diet composition and lower δ13C and δ³4S (δ¹³C = -33.02±2.66‰, δ³4S = -3.47±2.28‰; mean±1SD) compared to fish in the adjacent river (δ¹³C = -28.37±1.84‰, δ³4S = +2.23±2.25‰). These isotopic differences between habitats persisted across years of extreme droughts and floods. Despite the different diet composition, δ¹5N values from prey items on the floodplain (δ¹5N = 7.19±1.22‰) and river (δ¹5N = 7.25±1.46‰) were similar, suggesting similar trophic levels. The food web differences in δ13C and δ³4S between habitats were also reflected in salmon muscle tissue, reaching equilibrium between 24-30 days (2014, δ¹³C = -30.74±0.73‰, δ³4S = -4.6±0.68‰; 2016, δ¹³C = -34.74 ±0.49‰, δ³4S = -5.18±0.46‰). δ³4S measured in sequential growth bands in otoliths recorded a weekly time-series of shifting diet inputs, with the outermost layers recording time spent on the floodplain (δ³4S = -5.60±0.16‰) and river (δ³4S = 3.73±0.98‰). Our results suggest that δ¹³C and δ³4S can be used to differentiate floodplain and river rearing habitats used by native fishes, such as Chinook Salmon, across different hydrologic conditions and tissues. Together these stable isotope analyses provide a toolset to quantify the role of floodplains as fish habitats.

The Effect of Age-Related Macular Degeneration on Polarization Pattern Perception.

Purpose: The purpose of this study was to determine if a battery of polarization-modulated stimuli, quantified as a single metric, is effective in identifying macular disease in the presence/absence of cataract or pseudophakia. Methods: Using a modified liquid crystal display, polarization pattern perception (PPP) for a formulated battery of geometric and logMAR stimuli was evaluated in participants that had either no eye pathology (healthy participants) or were grouped according to the presence of cataract, pseudophakia, and/or age-related macular degeneration (AMD). PPP was quantified as response frequencies to individual stimuli, and as a novel monocular polarization sensitivity score (Ps) based on perception of the stimulus battery set. Results: Stimulus response frequencies were pattern-dependent and, compared with healthy participants, reduced for cataract and AMD groups but not for subjects with pseudophakia. Compared with healthy eyes (n = 47, median Ps = 17), Ps was significantly reduced by AMD (n = 59, median Ps = 1, P < 0.001) and, to a lesser extent, by cataracts (n = 80, median Ps = 6, P < 0.001). There was no significant difference between Ps for healthy and pseudophakic eyes (n = 47, median Ps = 13, P = 0.323). There was no significant correlation between Ps and logMAR visual acuity. Conclusions: In the absence of significant cataract, or in pseudophakia, a set of polarization-modulated visual stimuli, quantified as the Ps score, distinguishes AMD from healthy maculae. Translational Relevance: Perception of polarization-modulated stimuli, previously shown to be macula-dependent in a laboratory setting, is effective as a test of macular function in health and disease in a clinic setting.

The Clinical Application of Polarization Pattern Perception.

Purpose: Determine the repeatability of and optimum stimulus parameters for testing polarization pattern perception in a real-world clinical population, and assess the ability of polarization perception to distinguish normal from abnormal eyes. Methods: Polarization perception was evaluated in staff and patients attending ophthalmology clinics at Warwick Hospital, UK. A series of visual stimuli were presented in pseudorandom order using a liquid-crystal-display-based polarization pattern generator. Stimuli included geometric patterns, gratings, checkerboards, and optotypes. Participants had one or both eyes diagnosed as normal or abnormal following ophthalmic examination, optical coherence tomography, and measures of visual acuity. Measurement scores were assigned to the eye(s) of each participant depending on the total number of stimuli perceived or identified. Results: Stimuli covered the range of spatial scales resolvable within polarization perception by normal and abnormal eyes. Different stimuli had different saliencies. For each stimulus type, polarization perception in the abnormal group was significantly reduced compared with normal eyes (P < 0.001). Relative stimulus salience was broadly similar for normal-eye and abnormal-eye viewing groups, being greatest for radially symmetric patterns and least for optotypes. Checkerboard pattern salience had an inverse logarithmic relationship with check fundamental spatial frequency. A devised metric covering the dynamic range of polarization perception was repeatable, and the score derived from the metric was reduced in the abnormal group compared with the normal group (P < 0.001). Conclusions: Clinically useful metrics of polarization perception distinguish between normal and abnormal eyes. Translational Relevance: Perception of spatial patterns formed of non-uniform polarization fields has potential as a quantitative clinical diagnostic measurement.

Low serum 25-hydroxyvitamin D status in the pathogenesis of stress fractures in military personnel: An evidenced link to support injury risk management.

Stress fractures are common amongst healthy military recruits and athletes. Reduced vitamin D availability, measured by serum 25-hydroxyvitamin D (25OHD) status, has been associated with stress fracture risk during the 32-week Royal Marines (RM) training programme. A gene-environment interaction study was undertaken to explore this relationship to inform specific injury risk mitigation strategies. Fifty-one males who developed a stress fracture during RM training (n = 9 in weeks 1-15; n = 42 in weeks 16-32) and 141 uninjured controls were genotyped for the vitamin D receptor (VDR) FokI polymorphism. Serum 25OHD was measured at the start, middle and end (weeks 1, 15 and 32) of training. Serum 25OHD concentration increased in controls between weeks 1-15 (61.8±29.1 to 72.6±28.8 nmol/L, p = 0.01). Recruits who fractured did not show this rise and had lower week-15 25OHD concentration (p = 0.01). Higher week-15 25OHD concentration was associated with reduced stress fracture risk (adjusted OR 0.55[0.32-0.96] per 1SD increase, p = 0.04): the greater the increase in 25OHD, the greater the protective effect (p = 0.01). The f-allele was over-represented in fracture cases compared with controls (p<0.05). Baseline 25OHD status interacted with VDR genotype: a higher level was associated with reduced fracture risk in f-allele carriers (adjusted OR 0.39[0.17-0.91], p = 0.01). Improved 25OHD status between weeks 1-15 had a greater protective effect in FF genotype individuals (adjusted OR 0.31[0.12-0.81] vs. 1.78[0.90-3.49], p<0.01). Stress fracture risk in RM recruits is impacted by the interaction of VDR genotype with vitamin D status. This further supports the role of low serum vitamin D concentrations in causing stress fractures, and hence prophylactic vitamin D supplementation as an injury risk mitigation strategy.

Should Pearson's correlation coefficient be avoided?

PURPOSE: To survey the use of Pearson's correlation coefficient (r) and related statistical methods in the ophthalmic literature, to consider the limitations of r, and to suggest suitable alternative methods of analysis. RECENT FINDINGS: Searching Ophthalmic and Physiological Optics (OPO), Optometry and Vision Science (OVS), and Clinical and Experimental Optometry (CXO) online archives using correlation and Pearson's r as search terms resulted in 4057 and 281 hits respectively. Coefficient of determination, r square, or r squared received fewer hits (65, 8, and 22 hits respectively). The assumption that r follows a bivariate normal distribution was rarely encountered (3 hits) although several studies applied Spearman's rank correlation (70 hits). The intra-class correlation coefficient (ICC) was widely used (178 hits), but fewer hits were recorded for partial correlation (43 hits) and multiple correlation (13) hits. There was little evidence that the problem of sample size was addressed in correlation studies. SUMMARY: Investigators should be alert to whether: (1) the relationship between two variables could be non-linear, (2) the data are bivariate normal, (3) r accounts for a significant proportion of the variance in Y, (4) outliers are present, the data are clustered, or have a restricted range, (5) the sample size is appropriate, and (6) a significant correlation indicates causality. In addition, the number of significant digits used to express r and the problems of multiple testing should be addressed. The problems and limitations of r suggest a more cautious approach regarding its use and the application of alternative methods where appropriate.

The incidence of cardiac arrest in the intensive care unit: A systematic review and meta-analysis.

The incidence of cardiac arrest in the intensive care unit (ICU-CA) has not been widely reported. We undertook a systematic review and meta-analysis of studies reporting the incidence of cardiac arrest in adult, general intensive care units. The review was prospectively registered with PROSPERO (CRD42017079717). The search identified 7550 records, which included 20 relevant studies for qualitative analysis and 16 of these were included for quantitative analyses. The reported incidence of ICU-CA was 22.7 per 1000 admissions (95% CI: 17.4-29.6) with survival to hospital discharge of 17% (95% CI: 9.5-28.5%). We estimate that at least 5446 patients in the UK have a cardiac arrest after ICU admission. There are limited data and significant variation in the incidence of ICU-CA and efforts to synthesise these are limited by inconsistent reporting. Further prospective studies with standardised process and incidence measures are required to define this important patient group.

Calibrating temperature reconstructions from fish otolith oxygen isotope analysis for California's critically endangered Delta Smelt.

RATIONALE: Oxygen isotope ratios (δ18 O values) of fish otoliths (ear bones) are valuable geochemical tracers of water conditions and thermal life history. Delta Smelt (Hypomesus transpacificus) are osmerid forage fish endemic to the San Francisco Estuary, California, USA, that are on the verge of extinction. These fish exhibit a complex life history that allows them to survive in a dynamic estuarine environment; however, a rapidly warming climate threatens this thermally sensitive species. Here we quantify the accuracy and precision of using δ18 O values in otoliths to reconstruct the thermal life histories of Delta Smelt. METHODS: Delta Smelt were reared for 360 days using three different water sources with different ambient δ18 Owater values (-8.75‰, -5.28‰, and -4.06‰) and different water temperatures (16.4°C, 16.7°C, 18.7°C, and 20.5°C). Samples were collected after 170 days (n = 28) and 360 days (n = 14) post-hatch. In situ δ18 O values were measured from the core of the otolith to the dorsal edge using secondary ion mass spectrometry (SIMS) to reconstruct temporally resolved thermal life histories. RESULTS: The δ18 Ootolith values for Delta Smelt varied as a linear inverse function of water temperature: 1000 ln α = 18.39 (±0.43, 1SE)(103 TK-1 ) - 34.56 (±1.49, 1SE) and δ18 Ootolith(VPDB) - δ18 Owater (VPDB) = 31.34(±0.09, 1SE) - 0.19(±0.01, 1SE) × T ° C. When the ambient δ18 Owater value is known, this species-specific temperature-dependent oxygen isotope fractionation model facilitated the accurate (0.25°C) and precise (±0.37°C, 2σ) reconstruction of the water temperature experienced by the fish. In contrast, the use of existing general fractionation equations resulted in inaccurate temperature reconstructions. CONCLUSIONS: The species-specific δ18 Ootolith fractionation equation allowed for accurate and precise reconstructions of water temperatures experienced by Delta Smelt. Characterization of ambient δ18 Owater values remains a critical next step for reconstructing thermal life histories of wild Delta Smelt. This tool will provide new insights into habitat utilization, potential thermal refugia, and resilience to future warming for this critically endangered fish.

Successful non-operative management of haemodynamically unstable traumatic splenic injuries: 4-year case series in a UK major trauma centre.

PURPOSE: Management of traumatic splenic injury may be operative or non-operative (including embolization and conservative management). Traditionally, haemodynamic instability has been an indication for operative intervention. We aimed to report our experience of managing traumatic splenic injury at a regional major trauma centre in the UK over a 4-year period, with a particular focus on the non-operative management (NOM) of haemodynamically unstable patients. METHODS: All patients with splenic injuries admitted to North Bristol NHS Trust from April 2012 to March 2016 were included. Patients were classified for analyses by injury severity (low or high grade), haemodynamic instability (defined as a reverse shock index < 1) and management category (operative or non-operative). RESULTS: 106 patients were included. Overall 85.8% of patients received NOM: 79.2% conservative and 6.6% interventional radiology. Two patients (2.4%) managed conservatively required further intervention. Haemodynamically stable and unstable patients were equally likely to receive NOM (89.7 and 81.3% respectively, p = 1). All unstable patients with low-grade injuries were managed conservatively and only one (2.7%) required further intervention. Two unstable patients with high-grade injuries (28.6%) underwent NOM successfully. CONCLUSIONS: These data support the safe application of non-operative management to haemodynamically unstable patients with traumatic splenic injury, particularly in those with low-grade injuries. Additional prospective work is required to define the subgroup of patients for whom this is appropriate and to determine the long-term outcomes of NOM.

Type of Anesthesia for Endovascular Abdominal Aortic Aneurysm Repair.

OBJECTIVE: Endovascular aneurysm repair (EVAR) is used increasingly in the management of patients with abdominal aortic aneurysms (AAAs), including in the emergency setting for ruptured AAA. The lower mortality among patients undergoing emergency EVAR under local anesthesia (LA) observed in the Immediate Management of Patients with Rupture: Open Versus Endovascular Repair trial has sparked renewed interest in the anesthesia choice for EVAR. This systematic review evaluates the effect of mode of anesthesia on outcomes after EVAR. DESIGN: The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The primary outcome was in-hospital/30-day mortality, and both emergency and elective EVAR were included. The relative risk of death was estimated for each individual study without adjustment for potential confounding factors. SETTING: Hospitals. PARTICIPANTS: A total of 39,744 patients from 22 nonrandomized studies were included in the analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixteen studies in 23,202 patients compared LA to general anesthesia (GA) and reported in-hospital/30-day mortality. The unadjusted risk of death after emergency EVAR with LA was lower than with GA. Trends in elective surgery were less clear. CONCLUSION: There is some evidence across both emergency and elective settings to suggest that mode of anesthesia may be associated with improved outcomes. In particular, LA appears to have a positive effect on outcome after emergency EVAR. Because of the lack of randomized trial data, a significant risk of confounding remains. The optimal mode of anesthesia for EVAR should be investigated further and the reasons why particular anesthesia techniques are chosen for particular patients identified.

Cortical degeneration in chronic traumatic encephalopathy and Alzheimer's disease neuropathologic change.

OBJECTIVES: An observational study to compare the laminar distributions in frontal and temporal cortex of the tau-immunoreactive pathologies in chronic traumatic encephalopathy (CTE) and Alzheimer's disease neuropathologic change (ADNC). PATIENTS: Post-mortem material of (1) four cases of CTE without ADNC, (2) seven cases of CTE with ADNC (CTE/ADNC), and (3) seven cases of ADNC alone. RESULTS: In CTE and CTE/ADNC, neurofibrillary tangles (NFT), neuropil threads (NT), and dot-like grains (DLG) were distributed either in upper cortex or across all layers. Low densities of astrocytic tangles (AT) and abnormally enlarged neurons (EN) were not localized to any specific layer. Surviving neurons exhibited peaks of density in both upper and lower cortex, and vacuole density was greatest in superficial layers. In ADNC, neuritic plaques (NP) were more frequent, AT rare, NFT and NT were more widely distributed, NT affected lower layers more frequently, and surviving neurons were less frequently bimodal than in CTE and CTE/ADNC. CONCLUSION: Tau pathology in CTE and CTE/ADNC consistently affected the upper cortex but was more widely distributed in ADNC. The presence of CTE may encourage the development of ADNC pathology later in the course of the disease.

Topography of hemispheric white matter pathology in ten cases of neuronal intermediate filament inclusion disease.

AIMS: To characterize the topography of white matter pathology in neuronal intermediate filament inclusion disease (NIFID), a rare subtype of frontotemporal lobar degeneration (FTLD) with "fused in sarcoma" (FUS)-immunoreactive inclusions. MATERIAL AND METHODS: Fiber tracts from frontal and temporal lobes of 10 cases of NIFID. METHOD: Spatial patterns of the vacuolation, glial cell nuclei, and glial inclusions (GI) were studied across cortical fiber tracts from each case. RESULTS: Vacuoles and glial cells in NIFID were distributed either in regularly-distributed clusters or in large diffuse clusters contrasting with typical control cases in which smaller clusters of glial cells were surrounded by more compact clusters of vacuoles. Axonal varicosities and GI were also observed in the precentral gyrus (PCG) of 4 NIFID cases. Depending on region, the densities of glial cells and vacuoles were either positively or negatively spatially correlated, but there were no spatial correlations between the densities of the GI and either the vacuoles or glial cells. Spatial patterns in white matter were similar to those reported in adjacent gray matter. CONCLUSION: 1) Pathological changes across the white matter in NIFID are topographically distributed, 2) there is a correlation between the development of vacuolation and gliosis, and 3) white matter and gray matter pathologies are closely related.
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Visual problems associated with traumatic brain injury.

Traumatic brain injury (TBI) and its associated concussion are major causes of disability and death. All ages can be affected but children, young adults and the elderly are particularly susceptible. A decline in mortality has resulted in many more individuals living with a disability caused by TBI including those affecting vision. This review describes: (1) the major clinical and pathological features of TBI; (2) the visual signs and symptoms associated with the disorder; and (3) discusses the assessment of quality of life and visual rehabilitation of the patient. Defects in primary vision such as visual acuity and visual fields, eye movement including vergence, saccadic and smooth pursuit movements, and in more complex aspects of vision involving visual perception, motion vision ('akinopsia'), and visuo-spatial function have all been reported in TBI. Eye movement dysfunction may be an early sign of TBI. Hence, TBI can result in a variety of visual problems, many patients exhibiting multiple visual defects in combination with a decline in overall health. Patients with chronic dysfunction following TBI may require occupational, vestibular, cognitive and other forms of physical therapy. Such patients may also benefit from visual rehabilitation, including reading-related oculomotor training and the prescribing of spectacles with a variety of tints and prism combinations.

Visual Dysfunction in Parkinson's Disease.

This chapter describes the visual problems likely to be encountered in Parkinson's disease (PD) and whether such signs are useful in differentiating the parkinsonian syndromes. Visual dysfunction in PD may involve visual acuity, contrast sensitivity, color discrimination, pupil reactivity, saccadic and pursuit eye movements, motion perception, visual fields, and visual processing speeds. In addition, disturbance of visuospatial orientation, facial recognition problems, rapid eye movement (REM) sleep behavior disorder, and chronic visual hallucinations may be present. Problems affecting pupil reactivity, stereopsis, pursuit eye movement, and visuomotor adaptation, when accompanied by REM sleep behavior disorder, could be early features of PD. Dementia associated with PD is associated with enhanced eye movement problems, visuospatial deficits, and visual hallucinations. Visual dysfunction may be a useful diagnostic feature in differentiating PD from other parkinsonian symptoms, visual hallucinations, visuospatial dysfunction, and variation in saccadic eye movement problems being particularly useful discriminating features.