Faculty Bibliography

Importance/UNASSIGNED:In the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, acute treatment with clopidogrel-aspirin was associated with significantly reduced risk of recurrent stroke. There may be specific patient groups who are more likely to benefit from this treatment. Objective/UNASSIGNED:To investigate whether the association of clopidogrel-aspirin with stroke recurrence in patients with minor stroke or high-risk transient ischemic attack (TIA) is modified by the presence of infarct on imaging attributed to the index event (index imaging) among patients enrolled in the POINT Trial. Design, Setting, and Participants/UNASSIGNED:In the POINT randomized clinical trial, patients with high-risk TIA and minor ischemic stroke were enrolled at 269 sites in 10 countries in North America, Europe, Australia, and New Zealand from May 28, 2010, to December 19, 2017. In this post hoc analysis, patients were divided into 2 groups according to whether they had an acute infarct on index imaging. All POINT trial participants with information available on the presence or absence of acute infarct on index imaging were eligible for this study. Univariable Cox regression models evaluated associations between the presence of an infarct on index imaging and subsequent ischemic stroke and evaluated whether the presence of infarct on index imaging modified the association of clopidogrel-aspirin with subsequent ischemic stroke risk. Data were analyzed from July 2020 to May 2021. Exposures/UNASSIGNED:Presence or absence of acute infarct on index imaging. Main Outcomes and Measures/UNASSIGNED:The primary outcome is whether the presence of infarct on index imaging modified the association of clopidogrel-aspirin with subsequent ischemic stroke risk. Results/UNASSIGNED:Of the 4881 patients enrolled in POINT, 4876 (99.9%) met the inclusion criteria (mean [SD] age, 65 [13] years; 2685 men [55.0%]). A total of 1793 patients (36.8%) had an acute infarct on index imaging. Infarct on index imaging was associated with ischemic stroke during follow-up (hazard ratio [HR], 3.68; 95% CI, 2.73-4.95; P < .001). Clopidogrel-aspirin vs aspirin alone was associated with decreased ischemic stroke risk in patients with an infarct on index imaging (HR, 0.56; 95% CI, 0.41-0.77; P < .001) compared with those without an infarct on index imaging (HR, 1.11; 95% CI, 0.74-1.65; P = .62), with a significant interaction association (P for interaction = .008). Conclusions and Relevance/UNASSIGNED:In this study, the presence of an acute infarct on index imaging was associated with increased risk of recurrent stroke and a more pronounced benefit from clopidogrel-aspirin. Future work should focus on validating these findings before targeting specific patient populations for acute clopidogrel-aspirin treatment.

The care for the patients with end-stage heart failure has been revolutionized by the introduction of durable left ventricular assist devices, providing a substantial improvement in patient survival and quality of life and an alternative to heart transplantation. The newest devices have lower instances of mechanical dysfunction and associated pump thrombosis. Despite these improvements in complications, the use of continuous flow assist devices is still associated with high rates of thrombotic and hemorrhagic complications, most notably stroke in approximately 10% of continuous flow assist devices patients per year. With the newest HeartMate 3 devices, there have been lower observed rates of stroke, which has in part been achieved by both improvements in pump technology and knowledge of the risk factors for stroke and neurological complications. The therapeutic options available to clinicians to reduce the risk of stroke, including management of hypertension and antithrombotics, will be reviewed in this manuscript.

Background Vasospasm is a treatable cause of deterioration following aneurysmal subarachnoid hemorrhage. Cerebral computed tomography perfusion mean transit times have been proposed as a predictor of vasospasm but suffer from well-known technical limitations. We evaluated fully automated, thresholded time-to-maxima of the tissue residue function (T

Reconstructing intended speech from neural activity using brain-computer interfaces holds great promises for people with severe speech production deficits. While decoding overt speech has progressed, decoding imagined speech has met limited success, mainly because the associated neural signals are weak and variable compared to overt speech, hence difficult to decode by learning algorithms. We obtained three electrocorticography datasets from 13 patients, with electrodes implanted for epilepsy evaluation, who performed overt and imagined speech production tasks. Based on recent theories of speech neural processing, we extracted consistent and specific neural features usable for future brain computer interfaces, and assessed their performance to discriminate speech items in articulatory, phonetic, and vocalic representation spaces. While high-frequency activity provided the best signal for overt speech, both low- and higher-frequency power and local cross-frequency contributed to imagined speech decoding, in particular in phonetic and vocalic, i.e. perceptual, spaces. These findings show that low-frequency power and cross-frequency dynamics contain key information for imagined speech decoding.

BACKGROUND:Persistent cognitive symptoms have been reported following COVID-19 hospitalization. We investigated the relationship between demographics, social determinants of health (SDOH) and cognitive outcomes 6-months after hospitalization for COVID-19. METHODS:We analyzed 6-month follow-up data collected from a multi-center, prospective study of hospitalized COVID-19 patients. Demographic and SDOH variables (age, race/ethnicity, education, employment, health insurance status, median income, primary language, living arrangements, and pre-COVID disability) were compared between patients with normal versus abnormal telephone Montreal Cognitive Assessments (t-MOCA; scores<18/22). Multivariable logistic regression models were constructed to evaluate predictors of t-MoCA. RESULTS:Of 382 patients available for 6-month follow-up, 215 (56%) completed the t-MoCA (n = 109/215 [51%] had normal and n = 106/215 [49%] abnormal results). 14/215 (7%) patients had a prior history of dementia/cognitive impairment. Significant univariate predictors of abnormal t-MoCA included older age, ≤12 years of education, unemployment pre-COVID, Black race, and a pre-COVID history of cognitive impairment (all p < 0.05). In multivariable analyses, education ≤12 years (adjusted OR 5.21, 95%CI 2.25-12.09), Black race (aOR 5.54, 95%CI 2.25-13.66), and the interaction of baseline functional status and unemployment prior to hospitalization (aOR 3.98, 95%CI 1.23-12.92) were significantly associated with abnormal t-MoCA scores after adjusting for age, history of dementia, language, neurological complications, income and discharge disposition. CONCLUSIONS:Fewer years of education, Black race and unemployment with baseline disability were associated with abnormal t-MoCA scores 6-months post-hospitalization for COVID-19. These associations may be due to undiagnosed baseline cognitive dysfunction, implicit biases of the t-MoCA, other unmeasured SDOH or biological effects of SARS-CoV-2.

INTRODUCTION/BACKGROUND:Neurological complications among hospitalized COVID-19 patients may be associated with elevated neurodegenerative biomarkers. METHODS:Among hospitalized COVID-19 patients without a history of dementia (N = 251), we compared serum total tau (t-tau), phosphorylated tau-181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), and amyloid beta (Aβ40,42) between patients with or without encephalopathy, in-hospital death versus survival, and discharge home versus other dispositions. COVID-19 patient biomarker levels were also compared to non-COVID cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia controls (N = 161). RESULTS:Admission t-tau, p-tau181, GFAP, and NfL were significantly elevated in patients with encephalopathy and in those who died in-hospital, while t-tau, GFAP, and NfL were significantly lower in those discharged home. These markers correlated with severity of COVID illness. NfL, GFAP, and UCHL1 were higher in COVID patients than in non-COVID controls with MCI or AD. DISCUSSION/CONCLUSIONS:Neurodegenerative biomarkers were elevated to levels observed in AD dementia and associated with encephalopathy and worse outcomes among hospitalized COVID-19 patients.

OBJECTIVE:Despite the overall success of responsive neurostimulation (RNS) therapy for drug-resistant focal epilepsy, clinical outcomes in individuals vary significantly and are hard to predict. Biomarkers that indicate the clinical efficacy of RNS-ideally before device implantation-are critically needed, but challenges include the intrinsic heterogeneity of the RNS patient population and variability in clinical management across epilepsy centers. The aim of this study is to use a multicenter dataset to evaluate a candidate biomarker from intracranial electroencephalographic (iEEG) recordings that predicts clinical outcome with subsequent RNS therapy. METHODS:We assembled a federated dataset of iEEG recordings, collected prior to RNS implantation, from a retrospective cohort of 30 patients across three major epilepsy centers. Using ictal iEEG recordings, each center independently calculated network synchronizability, a candidate biomarker indicating the susceptibility of epileptic brain networks to RNS therapy. RESULTS:Ictal measures of synchronizability in the high-γ band (95-105 Hz) significantly distinguish between good and poor RNS responders after at least 3 years of therapy under the current RNS therapy guidelines (area under the curve = .83). Additionally, ictal high-γ synchronizability is inversely associated with the degree of therapeutic response. SIGNIFICANCE/CONCLUSIONS:This study provides a proof-of-concept roadmap for collaborative biomarker evaluation in federated data, where practical considerations impede full data sharing across centers. Our results suggest that network synchronizability can help predict therapeutic response to RNS therapy. With further validation, this biomarker could facilitate patient selection and help avert a costly, invasive intervention in patients who are unlikely to benefit.

OBJECTIVE:This study aims to determine the contributions of sun exposure and ultraviolet radiation (UVR) exposure to risk of paediatric-onset multiple sclerosis (MS). METHODS:Children with MS and controls recruited from multiple centres in the USA were matched on sex and age. Multivariable conditional logistic regression was used to investigate the association of time spent outdoors daily in summer, use of sun protection, and ambient summer UVR dose in the year prior to birth and the year prior to diagnosis, with MS risk, adjusting for sex, age, race, birth season, child's skin colour, mother's education, tobacco smoke exposure, being overweight, and Epstein-Barr virus infection. RESULTS:, 95%CI 0.62-0.94, p=0.01). CONCLUSIONS:If this is a causal association, spending more time in the sun during summer may be strongly protective against developing paediatric MS, as well as residing in a sunnier location.