Gray matter loss relates to dual task gait in Lewy body disorders and aging.

BACKGROUND: Within the spectrum of Lewy body disorders (LBD), both Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are characterized by gait and balance disturbances, which become more prominent under dual-task (DT) conditions. The brain substrates underlying DT gait variations, however, remain poorly understood in LBD. OBJECTIVE: To investigate the relationship between gray matter volume loss and DT gait variations in LBD. METHODS: Seventy-nine participants including cognitively unimpaired PD, PD with mild cognitive impairment, PD with dementia (PDD), or DLB and 20 cognitively unimpaired controls were examined across a multi-site study. PDD and DLB were grouped together for analyses. Differences in gait speed between single and DT conditions were quantified by dual task cost (DTC). Cortical, subcortical, ventricle, and cerebellum brain volumes were obtained using FreeSurfer. Linear regression models were used to examine the relationship between gray matter volumes and DTC. RESULTS: Smaller amygdala and total cortical volumes, and larger ventricle volumes were associated with a higher DTC across LBD and cognitively unimpaired controls. No statistically significant interaction between group and brain volumes were found. Adding cognitive and motor covariates or white matter hyperintensity volumes separately to the models did not affect brain volume and DTC associations. CONCLUSION: Gray matter volume loss is associated with worse DT gait performance compared to single task gait, across cognitively unimpaired controls through and the LBD spectrum. Impairment in DT gait performance may be driven by age-related cortical neurodegeneration.

Impacts of the COVID-19 Pandemic on the Healthcare Provision and Lived Experiences of Patients with Hydrocephalus.

The emergence of COVID-19 (SARS-CoV-2) led to distancing measures which acutely affected healthcare infrastructure, leading to limited in-person clinical visits and an increased number of virtual appointments. This study aimed to examine the effects this had on adults with hydrocephalus by describing the lived experiences of a cohort of patients at an outpatient hydrocephalus clinic. Between early May and early July of 2020, remote structured interviews were conducted with participants. Interviews were in-depth and open-ended, allowing participants to reflect and expand on the effects of the social distancing mandate on their well-being and quality of care. Three themes emerged: (1) impacts of changes in treatment provision, (2) impacts of changes in mitigating activities, and (3) impacts of changes on personal well-being. The comprehensive understanding of lived experiences may inform the future provision of healthcare services and social policy. Improved approaches to remote care telemedicine have the potential to facilitate high-quality care.

Cerebrovascular Reactivity Across the Entire Brain in Cerebral Amyloid Angiopathy.

BACKGROUND AND OBJECTIVES: Reduced cerebrovascular reactivity is proposed to be a feature of cerebral amyloid angiopathy (CAA) but has not been measured directly. Employing a global vasodilatory stimulus (hypercapnia), this study assessed the relationships between cerebrovascular reactivity and MRI markers of CAA and cognitive function. METHODS: In a cross-sectional study, individuals with probable CAA, mild cognitive impairment, or dementia due to Alzheimer disease and healthy controls underwent neuropsychological testing and an MRI that included a 5% carbon dioxide challenge. Cerebrovascular reactivity was compared across groups controlling for age, sex, and the presence of hypertension, and its associations with MRI markers of CAA in participants with CAA and with cognition across all participants were determined using multivariable linear regression adjusting for group, age, sex, education, and the presence of hypertension. RESULTS: Cerebrovascular reactivity data (mean ± SD) were available for 26 participants with CAA (9 female; 74.4 ± 7.7 years), 19 participants with mild cognitive impairment (5 female; 72.1 ± 8.5 years), 12 participants with dementia due to Alzheimer disease (4 female; 69.4 ± 6.6 years), and 39 healthy controls (30 female; 68.8 ± 5.4 years). Gray and whiter matter reactivity averaged across the entire brain was lower in participants with CAA and Alzheimer disease dementia compared to healthy controls, with a predominantly posterior distribution of lower reactivity in both groups. Higher white matter hyperintensity volume was associated with lower white matter reactivity (standardized coefficient [ß], 95% CI -0.48, -0.90 to -0.01). Higher gray matter reactivity was associated with better global cognitive function (ß 0.19, 0.03-0.36), memory (ß 0.21, 0.07-0.36), executive function (ß 0.20, 0.02-0.39), and processing speed (ß 0.27, 0.10-0.45) and higher white matter reactivity was associated with higher memory (ß 0.22, 0.08-0.36) and processing speed (ß 0.23, 0.06-0.40). CONCLUSIONS: Reduced cerebrovascular reactivity is a core feature of CAA and its assessment may provide an additional biomarker for disease severity and cognitive impairment.

Cortical Thickness and Its Association with Clinical Cognitive and Neuroimaging Markers in Cerebral Amyloid Angiopathy.

BACKGROUND: Cerebral amyloid angiopathy (CAA) contributes to brain neurodegeneration and cognitive decline, but the relationship between these two processes is incompletely understood. OBJECTIVE: The purpose of this study is to examine cortical thickness and its association with cognition and neurodegenerative biomarkers in CAA. METHODS: Data were collected from the Functional Assessment of Vascular Reactivity study and the Calgary Normative Study. In total, 48 participants with probable CAA, 72 cognitively normal healthy controls, and 24 participants with mild dementia due to AD were included. Participants underwent an MRI scan, after which global and regional cortical thickness measurements were obtained using FreeSurfer. General linear models, adjusted for age and sex, were used to compare cortical thickness globally and in an AD signature region. RESULTS: Global cortical thickness was lower in CAA compared to healthy controls (mean difference (MD) -0.047 mm, 95% confidence interval (CI) -0.088, -0.005, p = 0.03), and lower in AD compared to CAA (MD -0.104 mm, 95% CI -0.165, -0.043, p = 0.001). In the AD signature region, cortical thickness was lower in CAA compared to healthy controls (MD -0.07 mm, 95% CI -0.13 to -0.01, p = 0.02). Within the CAA group, lower cortical thickness was associated with lower memory scores (R2 = 0.10; p = 0.05) and higher white matter hyperintensity volume (R2 = 0.09, p = 0.04). CONCLUSION: CAA contributes to neurodegeneration in the form of lower cortical thickness, and this could contribute to cognitive decline. Regional overlap with an AD cortical atrophy signature region suggests that co-existing AD pathology may contribute to lower cortical thickness observed in CAA.

Diagnostic accuracy of clinical signs and symptoms for psychogenic nonepileptic attacks versus epileptic seizures: A systematic review and meta-analysis.

BACKGROUND: Psychogenic nonepileptic attacks (PNEA) are events of altered behavior that resemble epileptic seizures (ES) but are not caused by abnormal electrical cortical activity. Understanding which clinical signs and symptoms are associated with PNEA may allow better triaging for video-electroencephalogram monitoring (VEM) and for a more accurate prediction when such testing is unavailable. METHODS: We performed a systematic review searching Medline, Embase, and Cochrane Central from inception to March 29, 2019. We included original research that reported at least one clinical sign or symptom, included distinct groups of adult ES and PNEA with no overlap, and used VEM for the reference standard. Two authors independently assessed quality of the studies using the Quality Assessment of Diagnostic Accuracy Studies tool. Pooled estimates of sensitivity and specificity of studies were evaluated using a bivariate random effects model. RESULTS: We identified 4028 articles, of which 33 were included. There was a female sex predominance in the PNEA population (n = 22). From our meta-analysis, pooled sensitivities (0.27-0.72) and specificities (0.51-0.89) for PNEA were modest for individual signs. History of sexual abuse had the highest pooled specificity (89%), while the most sensitive feature was female sex (72%). Individual studies (n = 4) reported high levels of accuracy for ictal eye closure (sensitivity 64-73.7% and specificity 76.9-100%) and post-traumatic stress disorder (no reported sensitivity or specificity). Assuming the pre-test probability for PNEA in a tertiary care epilepsy center is 14%, even the strongest meta-analyzed features only exert modest diagnostic value, increasing post-test probabilities to a maximum of 33%. CONCLUSIONS: This review reflects the limited certainty afforded by individual clinical features to distinguish between PNEA and ES. Specific demographic and comorbid features, even despite moderately high specificities, impart minimal impact on diagnostic decision making. This emphasizes the need for the development of multisource predictive tools to optimize diagnostic likelihood ratios.

Examining the impacts of the COVID-19 pandemic on the well-being and virtual care of patients with epilepsy.

OBJECTIVE: The emergence of SARS-CoV-2 (COVID-19) as a novel coronavirus resulted in a global pandemic that necessitated the implementation of social distancing measures. These public health measures may have affected the provision of care for patients with epilepsy. Social isolation may have also adversely affected well-being and quality of life due to informal and formal support networks becoming less accessible. The purpose of this qualitative study was to examine the lived experiences of patients with epilepsy and to see how their quality of life and healthcare has been affected by the COVID-19 pandemic. METHODS: From April 27 to May 15, 2020 we performed remote interviews with 18 participants who had virtual appointments with their healthcare providers and were enrolled in the Calgary Comprehensive Epilepsy Program registry. Interviews were recorded and transcribed, after which transcripts were analyzed and coded into relevant themes using NVivo 12. RESULTS: Three broad themes emerged throughout the interviews:1) impact of pandemic on informal and formal support systems; 2) impact of pandemic on healthcare provision; and 3) concerns about the impact of the pandemic on personal situations and society in the future. Participants reported anxiety and stress about decreased social engagement and activity cessations. Although face-to-face appointments were preferred, virtual care was well-received. Common concerns about the future included securing employment and burnout from balancing family responsibilities. Some patients also feared they would be stigmatized as society adapted to the situation. SIGNIFICANCE: This study highlights the need for additional research in anticipation of the implementation of remote medicine in the management and treatment of epilepsy. It also highlights the tenacity of those living with epilepsy during difficult periods despite social and familial pressures. Raising awareness during this time about the lives and experiences of epilepsy patients can help challenge misconceptions and stigma in the workplace and wider society.

Cross-sectional and longitudinal differences in peak skeletonized white matter mean diffusivity in cerebral amyloid angiopathy.

OBJECTIVES: To test the hypotheses that peak skeletonized mean diffusivity (PSMD), a measure of cerebral white matter microstructural disruption, is 1) increased in patients with cerebral amyloid angiopathy (CAA) compared to normal control (NC), mild cognitive impairment (MCI), and Alzheimer's disease (AD); 2) associated with neuropsychological test performance among CAA patients; and 3) increased more quickly over one year in CAA than in AD, MCI, and NC. METHODS: Ninety-two participants provided a medical history, completed a neuropsychological assessment, and had a magnetic resonance (MR) exam including diffusion tensor imaging (DTI) from which PSMD was calculated. A 75-minute neuropsychological test battery was used to derive domain scores for memory, executive function, and processing speed. Multivariable analyses controlling for age and sex (and education, for cognitive outcomes) were used to test the study hypotheses. RESULTS: PSMD was higher in the CAA group (mean 4.97 × 10-4 mm2/s) compared to NC (3.25 × 10-4 mm2/s), MCI (3.62 × 10-4 mm2/s) and AD (3.89 × 10-4 mm2/s) groups (p < .01). Among CAA patients, higher PSMD was associated with slower processing speed (estimated -0.22 standard deviation (SD) change in processing speed z score per SD increase in PSMD, 95% CI -0.42 to -0.03, p = .03), higher WMH volume [ß = 0.74, CI 0.48 to 1.00], and higher CAA SVD score [ß = 0.68, CI 0.24 to 1.21] but was not associated with MMSE, executive function, memory, CMB count, or cortical thickness. PSMD increased over 1-year in all groups (p < .01) but without rate differences between groups (p = .66). CONCLUSIONS: PSMD, a simple marker of diffuse global white matter heterogeneity, is increased in CAA. Our findings further support a role for white matter disruption in causing cognitive impairment in CAA.

Medical assessment of potential concussion in elite football: video analysis of the 2016 UEFA European championship.

OBJECTIVE: The objective is to determine if suspected concussions in elite football are medically assessed according to the International Conferences on Concussion in Sport consensus statement recommendations. SETTING: Men's Union of European Football Association (UEFA) Football Championship. PARTICIPANTS: All professional football players in the UEFA 2016 Championship Tournament. DESIGN: Observational study. OUTCOME MEASURES: Potential concussive events (PCEs) were defined as direct head collision incidents resulting in the athlete being unable to immediately resume play following impact. PCEs identified and description of PCE assessment and outcome were accomplished through direct standardised observation of video footage by trained observers in 51 games played in the Men's UEFA European Championship (10 June-10 July 2016). RESULTS: Sixty-nine total PCEs (1.35 per match) were identified in 51 games played during the 2016 Men's UEFA European Championship. Forty-eight PCEs (69.6%) resulted in two observable signs of concussion, 13 (18.8%) resulted in three signs and 1 (1.4%) resulted in four signs in the injured athletes. Nineteen (27.5%) PCEs were medically assessed by sideline healthcare personnel while 50 (72.5%) were not. Of the 50 PCEs that were not medically assessed, 44 (88%) PCEs resulted in two or more signs of concussion among injured athletes. Of the 19 medically assessed PCEs, 8 resulted in 3 signs of concussion, and 1 resulted in 4 signs; all assessments concluded in the same-game return for the injured athletes. CONCLUSIONS: PCEs were frequent events in the 2016 UEFA Euro championship, but were rarely assessed concordant with the International Conferences on Concussion in Sport consensus statement recommendations. There is an imperative need to improve the assessment and management of players suspected of concussion in elite football.

Characteristics of the King-Devick test in the assessment of concussed patients in the subacute and later stages after injury.

Although the King-Devick (K-D) test has been used frequently in assessing sports related concussion early after injury, its characteristics over time after injury and in patients with prolonged persistent symptoms are unknown. The purpose of this paper was to: evaluate the ability of the K-D Test to distinguish patients seen early after concussion from those with symptoms persisting more than 3 months compared to controls, assess changes in the K-D test times over time after concussion, and determine the relationship of K-D times to the Stroop Color and Word Test scores. We performed cross-sectional comparisons of patients with recent concussive brain injury (acute group) and those with symptoms persisting more than 3 months to healthy controls on the K-D test, the Sports Concussion Assessment Tool 3 (SCAT3), and the Stroop Color and Word Test. Longitudinal comparisons of the acute group over time within the first month after injury were also made. Post-concussive syndrome (PCS) patients had significantly higher K-D times compared to controls (p = 0.01), while the acute group did not differ from controls(p = 0.33). K-D times at the second visit for the acute group were similar to those of controls (54.7 vs. 49.6, p = 0.31). While SCAT3 scores improved over time in the acute group, the K-D scores did not change between the first and second visit (55.2 vs. 54.7, p = 0.94). K-D scores correlated significantly with the Stroop scores for all three participant groups. The K-D test is likely useful very early after concussion in conjunction with baseline scores, and while scores in PCS patients remain elevated, they can be confounded by factors such as pre-morbid depression and medication use. High correlations with Stroop scores also suggest that performance on the K-D test can by proxy provide additional insight about cognitive function and predict performance on more cognitively demanding tasks.