Obstructive sleep apnea and white matter hyperintensities: correlation or causation?

Obstructive sleep apnea (apnea) is thought to cause small vessel ischemic episodes in the brain from hypoxic events, postulated as white matter hyperintensities (hyperintensities) identified on MRI which are implicated in cognitive decline. This study sought to evaluate these correlations. A retrospective evaluation of adults who underwent polysomnography (4/1/2016 to 4/30/2017) and a brain MRI prior to apnea diagnosis or within a year post-diagnosis was completed. MRI visual evaluation of hyperintensities using Fazekas scores were collected blind to clinical data. Collated clinical/MRI data were stratified and analyzed using chi-square, fishers t-tests, ANOVA/ANCOVA and linear regression. Stratification by apnea category revealed no significant differences in any variables including hyperintensity measures (Fazekas p=0.1584; periventricular p=0.3238; deep p=0.4618; deep total p=0.1770). Stratification by Fazekas category, periventricular and deep hyperintensities revealed increasing prevalence with age (p=0.0001); however, apnea categories were not significantly associated (Fazekas p=0.1479; periventricular p=0.3188; deep p=0.4503), nor were any individual apnea indicators. Continuous apnea measurements werre not associated with any hyperintensity factor; total deep hyperintensities were not associated with any apnea factors. Continuous BMI was not found to be associated with any apnea or hyperintensity factors. Only hypertension was noted to be associated with Fazekas (p=0.0045), deep (p=0.0010) and total deep (p=0.0021) hyperintensities; however, hypertension was not associated with apnea category (p=0.3038) or any associated factors. These data suggest apneas alone from OSA are insufficient to cause WMH, but other factors appear to contribute to the complex development of small vessel ischemic injury associated with age and cognitive decline.

Characterization of chondroitinase-induced lumbar intervertebral disc degeneration in a sheep model intended for assessing biomaterials.

Intervertebral disc (IVD) degeneration (IVDD) leads to structural and functional changes. Biomaterials for restoring IVD function and promoting regeneration are currently being investigated; however, such approaches require validation using animal models that recapitulate clinical, biochemical, and biomechanical hallmarks of the human pathology. Herein, we comprehensively characterized a sheep model of chondroitinase-ABC (ChABC) induced IVDD. Briefly, ChABC (1 U) was injected into the L1/2 , L2/3 , and L3/4 IVDs. Degeneration was assessed via longitudinal magnetic resonance (MR) and radiographic imaging. Additionally, kinematic, biochemical, and histological analyses were performed on explanted functional spinal units (FSUs). At 17-weeks, ChABC treated IVDs demonstrated significant reductions in MR index (p = 0.030) and disc height (p = 0.009) compared with pre-operative values. Additionally, ChABC treated IVDs exhibited significantly increased creep displacement (p = 0.004) and axial range of motion (p = 0.007) concomitant with significant decreases in tensile (p = 0.034) and torsional (p = 0.021) stiffnesses and long-term viscoelastic properties (p = 0.016). ChABC treated IVDs also exhibited a significant decrease in NP glycosaminoglycan: hydroxyproline ratio (p = 0.002) and changes in microarchitecture, particularly in the NP and endplates, compared with uninjured IVDs. Taken together, this study demonstrated that intradiscal injection of ChABC induces significant degeneration in sheep lumbar IVDs and the potential for using this model in evaluating biomaterials for IVD repair, regeneration, or fusion.

Patients Encounter as a Motivating Factor for Academic Performance in a Medical Neuroscience Course.

BACKGROUND: The integration of patient encounters into the first year of the medical school curriculum is known to be of vital importance in the development of critical thinking and communication skills. We investigated whether exposure of first year medical students to patient encounters during a first year medical school neuroscience course result in a high level of motivation associated with the clinical encounter, and whether this high level of motivation translates to higher academic performance as measured by their performance on formative and summative examinations. METHODS: First year medical students interacted with patients presenting with different neurological disorders in a small group informal session. Following the small group interactions with patients, students participated in a large group debriefing session involving discussions with peers, biomedical sciences faculty, and clinicians. Students then completed a survey designed to assess their motivation in correspondence with the Attention, Relevance, Confidence, and Satisfaction (ARCS) model of motivation. These results were then correlated with students' performance in the neuroscience examinations. RESULTS: The total mean score was high for all categories of the ARCS model of motivation (4.26/5) and was highest for Relevance (4.46/5). When these motivation scores were correlated with students' performance on the formative and summative examinations, a significant positive correlation was found between motivation and performance on both the formative (r = 0.85) and summative (r = 0.95) neuroscience examinations. CONCLUSION: Encounters with patients presenting with neurological disorders during a first year medical neuroscience course result in a high level of motivation associated with the clinical encounter, and this was positively correlated with their academic performance.

The Impact of Meeting Patients with Neurological Disorders on Medical Student Empathy.

PURPOSE: Empathy tends to decline during medical education, typically beginning in the third year of medical school and often continuing throughout residency and the physician's medical career. The purpose of this study was to determine if first year medical student empathy is affected by small group interactions with patients with neurological disorders, and to investigate if changes in empathy persisted over time. MATERIALS AND METHODS: Eighty first year medical students participating in a Neuroscience Module interacted with a variety of neurological patients in a small group informational session. Prior to the experience, participants completed the Jefferson Scale of Physician Empathy-Student (JSPE-S) version. After the experience, students completed a post-test JSPE-S questionnaire, and a final post-post-test JSPE-S questionnaire was completed 5 weeks later. Empathy scores were compared with a repeated measures MANOVA. The relationship between gender and empathy, and the effect of the age of the neurological patients on empathy scores were also examined. RESULTS: Empathy scores for seventy-one students who completed the JSPE-S questionnaires were analyzed. Students had significantly higher empathy immediately after the patient interaction experience, and the change in empathy was sustained over the course of 5 weeks (p = 0.015). The age of the neurological patients had a significant effect on empathy scores. There was no significant difference between empathy scores and gender. CONCLUSIONS: This study supports the incorporation of a group patient interaction experience into the medical school curriculum as an inexpensive and practical method of enhancing medical student empathy in a non-clinical setting.

Acanthamoeba spp. and Balamuthia mandrillaris leading to fatal granulomatous amebic encephalitis.

Acanthamoeba spp. and Balamuthia mandrillaris are free-living amebae known to cause disseminated and fatal central nervous system dysfunction which manifests as granulomatous amebic encephalitis (GAE) with exceedingly rare frequency. We report two lethal cases of infection with free-living amebae: an acute case of Acanthamoeba spp. infection in an immunocompromised female and a subacute case of B. mandrillaris in a Hispanic male. The Acanthamoeba spp. infection presented with an atypical lesion in the thalamus that caused rapid deterioration of the patient while the case of B. mandrillaris had a prolonged clinical course with multifocal lesions beginning in the frontal lobe. Cerebrospinal fluid results were non-specific in both cases, however, post-mortem histology demonstrated the presence of trophozoites along a perivascular distribution of necrosis and infiltrate composed primarily of neutrophils. In addition to detailing the clinical presentations of these infrequent amebic infections, we offer insight into the difficulties surrounding their diagnoses in order to aid the clinician in accurate and timely identification.

Sequential effects of reappraisal and rumination on anger during recall of an anger-provoking event.

In everyday life, people often combine strategies to regulate their emotions. However, to date, most research has investigated emotion regulation strategies as if they occur independently from one another. The current study aims to better understand the sequential interplay between strategies by investigating how reappraisal and rumination interact to affect anger experience. After participants (N = 156) recalled a recent anger-provoking event, they were instructed to either a) reappraise the event twice, b) reappraise the event, and then ruminate about the event, c) ruminate about the event, and then reappraise the event, or d) ruminate twice about the event. The effects of the first strategy used replicated a large body of research: reappraisal was associated with a decrease in anger, but rumination was associated with no change in anger. There was a small interactive effect of the combination of the two strategies, such that those who ruminated and then reappraised showed a larger decrease in anger than those who reappraised and then ruminated. There were no other differences between groups. This suggests that the second strategy does have an effect over and beyond the first strategy, but this effect is small in size, highlighting the importance of the initial emotion regulation strategy used.

Stroke and dyslipidemia: clinical risk factors in the telestroke versus non-telestroke.

BACKGROUND: Clinical risk factors related to not administering thrombolysis to acute ischemic stroke patients with incidence dyslipidemia is not clear. This issue was investigated in telestroke and non-telestroke settings. METHODS: We analyzed retrospective data collected from a stroke registry to compare exclusion risk factors in the telestroke and non-telestroke. We performed multivariate analysis was performed to identify risk factors that may result in exclusion from rtPA. Variance inflation factors were used to examine multicollinearity and significant interactions between independent variables in the model, while Hosmer-Lemeshow test, Cox & Snell were used to determine the fitness of the regression models. RESULTS: A greater number of patients with acute ischemic stroke with incidence dyslipidemia were treated in the non-telestroke (285) when compared with the telestroke network (187). Although non-telestroke admitted more patients than the telestroke, the telestroke treated more patients with rtPA (89.30%) and excluded less (10.70%), while the non-telestroke excluded from rtPA (61.40%). In the non-telestroke, age (adjusted OR, 0.965; 95% CI, 0.942-0.99), blood glucose level (adjusted OR, 0.995; 95% CI, 0.99-0.999), international normalized ratio (adjusted OR, 0.154; 95% CI, 0.031-0.78),congestive heart failure(CHF) (adjusted OR, 0.318; 95% CI, 0.109-0.928), previous stroke (adjusted OR, 0.405; 95% CI, 0.2-0.821) and renal insufficiency (adjusted OR, 0.179; 95% CI, 0.035-0.908) were all directly linked to exclusion from rtPA. In the telestroke, only body mass index (adjusted OR, 0.911; 95% CI, 0.832-0.997) significantly excluded acute ischemic stroke patients with incidence dyslipidemia from thrombolysis therapy. CONCLUSION: Despite having more patients with acute ischemic stroke that present incidence dyslipidemia, the non-telestroke patients had more clinical risk factors that excluded more patients from rtPA when compared with telestroke. Future studies should focus on how identified clinical risk factors can be managed to improve the use of rtPA in the non-telestroke setting. Moreover, the optimization of the risk-benefit ratio of rtPA by the telestroke technology can be advanced to the non-telestroke setting to improve the use of thrombolysis therapy.

Functional Outcome Measures of Recombinant Tissue Plasminogen Activator-Treated Stroke Patients in the Telestroke Technology.

The efficiency of telestroke programs in improving the rates of recombinant tissue plasminogen activator (rtPA) in stroke patients has been reported. Previous studies have reported favorable treatment outcomes with the use of telestroke programs to improve the use of rtPA, but functional outcomes are not fully understood. This study investigated the effect of telestroke technology in the administration of rtPA and related functional outcomes associated with baseline clinical variables. Retrospective data of a telestroke registry were analyzed. Univariate analysis was used to compare demographic and clinical variables in the rtPA group and the no rtPA group and between the improved functional ambulation group and the no improvement group. A stepwise binary logistic regression identified factors associated with improved functional outcome in the total telestroke population and in the subset of the telestroke population who received rtPA. In adjusted analysis and elimination of any multicollinearity for patients who received rtPA in the telestroke setting, obesity (odds ratio [OR] = 2.138, 95% confidence interval [CI], 1.164-3.928, P < .05), higher systolic blood pressure at the time of presentation (OR = 1.015, 95% CI, 1.003-1.027, P < .05), and baseline high-density lipoprotein at the time of admission (OR = 1.032, 95% CI, 1.005-1.059, P < .05) were associated with improved functional outcomes. Increasing age (OR = 0.940, 95% CI, 0.916-0.965, P < .0001) and higher calculated National Institutes of Health Stroke Scale (OR = 0.903, 95% CI, 0.869-0.937) were associated with a poorer outcome in rtPA-treated patients. Telestroke technology improves functional outcomes at spoke stations where neurological expertise is unavailable. Further studies are necessary to determine how telestroke technology can be optimized, especially to improve contraindications and increase eligibility for thrombolysis therapy.

Clinical Risk Factors in Thrombolysis therapy: Telestroke Versus Nontelestroke.

BACKGROUND: The objective of this study is to determine clinical risk factors associated with exclusion from thrombolysis in telestroke and nontelestroke settings. These risk factors may offer clues for optimization of thrombolysis therapy in acute ischemic stroke population. MATERIALS AND METHODS: Retrospective data of patients with acute ischemic stroke via telestroke and nontelestroke assessment were analyzed. Univariate analysis was used to compare the recombinant tissue plasminogen activator (rtPA) group and the no rtPA group. A stepwise binary logistic regression identified factors associated with inclusion and exclusion from rtPA in the total telestroke population and the subsets of the telestroke population. RESULTS: Telestroke patients were more likely to be directly admitted rather than being initially evaluated in the emergency department (70.3% versus 9.9%) and were also substantially more likely to receive rtPA (89.5% versus 38.5%). In the nontelestroke group, patients with acute ischemic stroke were more likely to be excluded from rtPA if they possessed higher international normalized ratios (odds ratio [OR] = 4.978 [1.503-16.488]) or had a history of congestive heart failure (OR = 2.524 [1.213-5.252]), previous stroke (OR = 2.172 [1.286-3.667]), or renal dysfunction (OR = 4.204 [1.33-13.281]). The telestroke group only had 1 variable deemed statistically significant in its association with rtPA status. Patients who were directly admitted were less likely to be excluded from receipt of rtPA (OR = .322 [.112-0.927]). CONCLUSIONS: Factors associated with exclusion from rtPA in the nontelestroke setting did not exclude patients with acute ischemic stroke from thrombolysis therapy in the telestroke setting. Telestroke may offer methods for optimization of the risk-benefit ratio of rtPA, equipping clinicians to efficiently make treatment decisions.

In a stroke cohort with incident hypertension; are more women than men likely to be excluded from recombinant tissue-type Plasminogen Activator (rtPA)?

BACKGROUND: The treatment outcomes in the use of rt-PA have been reported. Some studies reported worse outcome in women than men, while others presented opposing data. Using data from a hospital-based stroke registry, we investigated evidence of gender difference and determined exclusion criteria in a stroke population with incidence of hypertension. METHOD: In a stroke population of women and men with incident of hypertension from a stroke registry, demographics and clinical factors were compared. Univariate analysis was used to determine gender differences, while multivariable models adjusted for demographic and clinical variables. RESULTS: Among the 669 stroke patients with incident of hypertension that were excluded from rt-PA treatment, 362 were female and 307 were male. Female patients with increasing age (OR = 0.956-0.984, P < 0.001), diabetes mellitus (OR = 0.095-0.559, P = 0.001), higher NIH stroke scale score (OR = 1.019-1.090, P = 0.002), previous stroke (OR = 0.337-0.850, P = 0.008), diabetes medication (OR = 1.200-7.724, P = 0.019), and INR (OR = 0.033-0.597, P = 0.008) are more likely to be excluded. Male patients with a history of a previous stroke (OR = 0.265-0.704, P = 0.001), risk of mortality (OR = 0.803-0.950, P = 0.002), higher NIH stroke scale score(OR = 1.101-1.276, P < 0.001), cholesterol reducing medication (OR = 1.191-2.910, P = 0.006), weakness at presentation(OR = 1.207-4.421, P = 0.011), and INR (OR = 0.016-0.243, P < 0.001) are more likely to be excluded. CONCLUSION: Women have a worse outcome than men in an untreated acute ischemic stroke population, but when treated, women have a better treatment outcome compared to men. In a hypertensive stroke population, the clinical variables for the exclusion criteria for women and men are significantly different, even after adjustment for confounding variables.

Pharmacological thrombolysis for acute ischemic stroke treatment: Gender differences in clinical risk factors.

BACKGROUND: In a stroke population, women have a worse outcome than men when untreated. In contrast, there is no significant difference in treated patients. In this study, we determined whether clinical variables represent a promising approach to assist in the evaluation of gender differences in a stroke population. METHODS: We analyzed data from ischemic stroke patients' ≥18 years-old from the stroke registry on rtPA administration and identified gender differences in clinical factors within inclusion and exclusion criteria in a stroke population that received rtPA. Multivariate analysis was used to adjust for patient demographic and clinical variables. RESULTS: Of the 241 eligible stroke patients' thrombolytic therapy, 49.4% were females and 50.6% were males. Of the 422 patients that did not receive rtPA, more women (235) were excluded from rtPA than men (187) (P<0.05). In the male population, exclusion from rtPA was associated with history of a previous stroke (P<0.05, OR=2.028), hypertension (P<0.05, OR=0.519), and NIH stroke score (P<0.0001, OR=0.893). In female stroke patients, exclusion from rtPA was associated with previous history of stroke (P<0.05, OR=2.332), diabetes (P<0.05, OR=1.88) and NIH stroke score (P<0.05, OR=0.916). CONCLUSIONS: Despite similarities in different areas of stroke care for both men and women, more women with diabetes, previous history of stroke and higher NIH scores are more likely to be excluded from thrombolytic therapy. Men with a previous history of stroke, hypertension and higher NIH scores are more likely to be excluded rtPA even after adjustment for confounding variables.

Perceived social pressure not to experience negative emotion is linked to selective attention for negative information.

Social norms and values may be important predictors of how people engage with and regulate their negative emotional experiences. Previous research has shown that social expectancies (the perceived social pressure not to feel negative emotion (NE)) exacerbate feelings of sadness. In the current research, we examined whether social expectancies may be linked to how people process emotional information. Using a modified classical flanker task involving emotional rather than non-emotional stimuli, we found that, for those who experienced low levels of NE, social expectancies were linked to the selective avoidance of negative emotional information. Those who experienced high levels of NE did not show a selective avoidance of negative emotional information. The findings suggest that, for people who experience many NEs, social expectancies may lead to discrepancies between how they think they ought to feel and the kind of emotional information they pay attention to.

The cognitive building blocks of emotion regulation: ability to update working memory moderates the efficacy of rumination and reappraisal on emotion.

The ability to regulate emotions is a critical component of healthy emotional functioning. Therefore, it is important to determine factors that contribute to the efficacy of emotion regulation. The present article examined whether the ability to update emotional information in working memory is a predictor of the efficacy of rumination and reappraisal on affective experience both at the trait level (Study 1) and in daily life (Study 2). In both studies, results revealed that the relationship between use of reappraisal and high arousal negative emotions was moderated by updating ability. Specifically, use of reappraisal was associated with decreased high arousal negative emotions for participants with high updating ability, while no significant relationship was found for those with low updating ability. In addition, both studies also revealed that the relationship between rumination and high arousal negative emotions was moderated by updating ability. In general, use of rumination was associated with elevated high arousal negative emotions. However, this relationship was blunted for participants with high updating ability. That is, use of rumination was associated with less elevated high arousal negative emotions for participants with high updating ability. These results identify the ability to update emotional information in working memory as a crucial process modulating the efficacy of emotion regulation efforts.

A diffusion model account of the relationship between the emotional flanker task and rumination and depression.

Although there exists a consensus that depression is characterized by preferential processing of negative information, empirical findings to support the association between depression and rumination on the one hand and selective attention for negative stimuli on the other hand have been elusive. We argue that one of the reasons for the inconsistent findings may be the use of aggregate measures of response times and accuracies to measure attentional bias. Diffusion model analysis allows to partial out the information processing component from other components that comprise the decision-making process. In this study, we applied a diffusion model to an emotional flanker task. Results revealed that when focusing on a negative target, both rumination and depression were associated with facilitated processing due to negative distracters, whereas only rumination was associated with less interference by positive distracters. After controlling for depression scores, rumination still predicted attentional bias for negative information, but depression scores were no longer predictive after controlling for rumination. Consistent with elusive findings in the literature, we did not find this pattern of results when using accuracy scores or mean response times. Our results suggest that rumination accounts for the attentional bias for negative information found in depression.

Executive well-being: updating of positive stimuli in working memory is associated with subjective well-being.

A growing literature shows that the ability to control affective information in working memory (WM) plays an important role in emotional functioning. Whereas most studies have focused on executive processes relating to emotion dysregulation and mood disorders, few, if any, have looked at such processes in association with happiness. In this study, we examined whether the ability to update positive and negative stimuli in WM (assessed with an affective n-back task) is related to the cognitive and affective components of subjective well-being. Participants who were better at retaining and updating specifically positive (not negative) information in WM displayed higher levels of life satisfaction and affect balance, both at the trait level and in daily life. These results suggest that effective updating of positive information in WM may underlie happy people's ability to maintain and further enhance positive thoughts and emotions.

Interference resolution moderates the impact of rumination and reappraisal on affective experiences in daily life.

Research has shown that cognitive control processes play a central role in emotion regulation. While most research has examined whether individual differences in such processes are related to the use of these strategies, a crucial next step involves examining whether such differences influence their impact on people's feelings, especially in normal daily life. The present study examined whether impairments in cognitive control (measured using an affective interference resolution task) moderate the impact of using rumination and reappraisal on affective experiences in everyday life (assessed using experience sampling methods). Multilevel analyses revealed that difficulties removing previously relevant negative information from working memory were associated with a larger increase in negative affect following rumination, and smaller increase and decrease in positive and negative affect, respectively, following reappraisal. These findings show that impaired interference resolution for negative information aggravates the deleterious effects of rumination and curbs the benefits of reappraisal in daily life.

The dynamic interplay between emotions in daily life: augmentation, blunting, and the role of appraisal overlap.

Our emotions don't have lives of their own, but mutually influence each other across time. Augmentation and blunting occur when experience of a current emotion increases or decreases the experience of another, subsequent emotion, and play a role in many everyday phenomena. In this study, we investigated patterns of augmentation and blunting between the experience of anger, sadness, relaxation, and happiness in daily life. In general, emotions with similar (opposite) valence showed augmentation (blunting) from one moment to the next. In search for a possible underlying mechanism, we showed that strength of augmentation and blunting was a function of degree of idiosyncratic appraisal overlap between two emotional states. This occurred even to the point that emotions with similar valence blunted one another in cases of small overlap, and emotions with opposite valence augmented one another in cases of large overlap. The findings reveal the dynamic interplay between different emotions across time, and highlight the role of appraisal overlap therein.

The cognitive underpinnings of emerging mathematical skills: executive functioning, patterns, numeracy, and arithmetic.

BACKGROUND: Exposure to mathematical pattern tasks is often deemed important for developing children's algebraic thinking skills. Yet, there is a dearth of evidence on the cognitive underpinnings of pattern tasks and how early competencies on these tasks are related to later development. AIMS: We examined the domain-specific and domain-general determinants of performances on pattern tasks by using (a) a standardized test of numerical and arithmetic proficiency and (b) measures of executive functioning, respectively. SAMPLE: Participants were 163 6-year-olds enrolled in primary schools that typically serve families from low to middle socioeconomic backgrounds. METHOD: Children were administered a battery of executive functioning (inhibitory, switching, updating), numerical and arithmetic proficiency (the Numerical Operations task from the Wechsler Individual Achievement Test-II), and three types of pattern tasks. RESULTS: Contrary to findings from the adult literature, we found all the executive functioning measures coalesced into two factors: updating and an inhibition/switch factor. Only the updating factor predicted performances on the pattern tasks. Although performance on the pattern tasks were correlated with numerical and arithmetic proficiency, findings from structural equation modelling showed that there were no direct or independent relationships between them. CONCLUSIONS: The findings suggest that the bivariate relationships between pattern, numeracy, and arithmetic tasks are likely due to their shared demands on updating resources. Unlike older children, these findings suggest that for 6-year-olds, better numerical and arithmetic proficiency, without accompanying advantages in updating capacities, will no more likely lead to better performance on the pattern tasks.