Recent Vitamin K Antagonist Use and Intracranial Hemorrhage After Endovascular Thrombectomy for Acute Ischemic Stroke.

Importance: Use of oral vitamin K antagonists (VKAs) may place patients undergoing endovascular thrombectomy (EVT) for acute ischemic stroke caused by large vessel occlusion at increased risk of complications. Objective: To determine the association between recent use of a VKA and outcomes among patients selected to undergo EVT in clinical practice. Design, Setting, and Participants: Retrospective, observational cohort study based on the American Heart Association's Get With the Guidelines-Stroke Program between October 2015 and March 2020. From 594 participating hospitals in the US, 32 715 patients with acute ischemic stroke selected to undergo EVT within 6 hours of time last known to be well were included. Exposure: VKA use within the 7 days prior to hospital arrival. Main Outcome and Measures: The primary end point was symptomatic intracranial hemorrhage (sICH). Secondary end points included life-threatening systemic hemorrhage, another serious complication, any complications of reperfusion therapy, in-hospital mortality, and in-hospital mortality or discharge to hospice. Results: Of 32 715 patients (median age, 72 years; 50.7% female), 3087 (9.4%) had used a VKA (median international normalized ratio [INR], 1.5 [IQR, 1.2-1.9]) and 29 628 had not used a VKA prior to hospital presentation. Overall, prior VKA use was not significantly associated with an increased risk of sICH (211/3087 patients [6.8%] taking a VKA compared with 1904/29 628 patients [6.4%] not taking a VKA; adjusted odds ratio [OR], 1.12 [95% CI, 0.94-1.35]; adjusted risk difference, 0.69% [95% CI, -0.39% to 1.77%]). Among 830 patients taking a VKA with an INR greater than 1.7, sICH risk was significantly higher than in those not taking a VKA (8.3% vs 6.4%; adjusted OR, 1.88 [95% CI, 1.33-2.65]; adjusted risk difference, 4.03% [95% CI, 1.53%-6.53%]), while those with an INR of 1.7 or lower (n = 1585) had no significant difference in the risk of sICH (6.7% vs 6.4%; adjusted OR, 1.24 [95% CI, 0.87-1.76]; adjusted risk difference, 1.13% [95% CI, -0.79% to 3.04%]). Of 5 prespecified secondary end points, none showed a significant difference across VKA-exposed vs VKA-unexposed groups. Conclusions and Relevance: Among patients with acute ischemic stroke selected to receive EVT, VKA use within the preceding 7 days was not associated with a significantly increased risk of sICH overall. However, recent VKA use with a presenting INR greater than 1.7 was associated with a significantly increased risk of sICH compared with no use of anticoagulants.

Fronto-Parietal and White Matter Haemodynamics Predict Cognitive Outcome in Children with Moyamoya Independent of Stroke.

Moyamoya disease is a major arteriopathy characterised by progressive steno-occlusion of the arteries of the circle of Willis. Studies in adults with moyamoya suggest an association between abnormal fronto-parietal and white matter regional haemodynamics and cognitive impairments, even in the absence of focal infarction. However, these associations have not been investigated in children with moyamoya. We examined the relationship between regional haemodynamics and ratings of intellectual ability and executive function, using hypercapnic challenge blood oxygen level-dependent magnetic resonance imaging of cerebrovascular reactivity in a consecutive cohort of children with confirmed moyamoya. Thirty children were included in the final analysis (mean age: 12.55 ± 3.03 years, 17 females, 15 idiopathic moyamoya and 15 syndromic moyamoya). Frontal haemodynamics were abnormal in all regardless of stroke history and comorbidity, but occipital lobe haemodynamics were also abnormal in children with syndromic moyamoya. Executive function deficits were noted in both idiopathic and syndromic moyamoya, whereas intellectual ability was impaired in syndromic moyamoya, even in the absence of stroke. Analysis of the relative effect of regional abnormal haemodynamics on cognitive outcomes demonstrated that executive dysfunction was predominantly explained by right parietal and white matter haemodynamics independent of stroke and comorbidity, while posterior circulation haemodynamics predicted intellectual ability. These results suggest that parietal and posterior haemodynamics play a compensatory role in overcoming frontal vulnerability and cognitive impairment.

Distinct Clinical and Radiographic Phenotypes in Pediatric Patients With Moyamoya.

BACKGROUND: Given the expanding evidence of clinico-radiological differences between moyamoya disease (MMD) and moyamoya syndrome (MMS), we compared the clinical and radiographic features of childhood MMD and MMS to identify predictors of ischemic event recurrence. METHODS: We reviewed a pediatric moyamoya cohort followed between 2003 and 2019. Clinical and radiographic characteristics at diagnosis and follow-up were abstracted. Comparisons between MMD and MMS as well as between MMD and two MMS subgroups (neurofibromatosis [MMS-NF1] and sickle cell disease [MMS-SCD]) were performed. RESULTS: A total of 111 patients were identified. Patients with MMD presented commonly with transient ischemic attacks (TIAs) (35 % MMD versus 13% MMS-NF1 versus 9.5% MMS-SCD; P = 0.047). Symptomatic stroke presentation (MMD 37% versus MMS-NF1 4% versus 33%; P = 0.0147) and bilateral disease at diagnosis (MMD 73% versus MMS-NF1 22 % versus MMS-SCD 67%; P = 0.0002) were uncommon in MMS-NF1. TIA recurrence was common in MMD (hazard ratio 2.86; P = 0.001). The ivy sign was absent on neuroimaging in a majority of patients with MMS-SCD (MMD 67% versus MMS-NF1 52% versus MMS-SCD 9.5%; P = 0.0002). Predictors of poor motor outcome included early age at diagnosis (odds ratio [OR] 8.45; P = 0.0014), symptomatic stroke presentation (OR 6.6; P = 0.019), and advanced Suzuki stage (OR 3.59; P = 0.019). CONCLUSIONS: Moyamoya exhibits different phenotypes based on underlying etiologies. Frequent TIAs is a common phenotype of MMD and symptomatic stroke presentation a common feature of MMD and MMS-SCD, whereas unilateral disease and low infarct burden are common in MMS-NF1. In addition, absence of ivy sign is a common phenotype in MMS-SCD.

PANDAS/PANS in childhood: Controversies and evidence.

Since first defined in 1998, paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and its later, broader iteration, paediatric acute-onset neuropsychiatric syndrome (PANS), have garnered significant attention and controversy. The role of streptococcal infection in children with explosive onset obsessive-compulsive disorder and new onset tics, the natural history of this entity, and the role of symptomatic and disease-modifying therapies, including antibiotics, immunotherapy, and psychoactive drugs, are all issues that have yet to be definitively addressed. While definitive proof of the autoimmune hypothesis of PANDAS is lacking, given the heightened attention to this entity and apparent rise in use of this diagnostic category, addressing questions around diagnosis, treatment, and etiology is imperative. In this paper, we review current working definitions of PANDAS/PANS, discuss published evidence for interventions related to this entity, and propose a clinical approach to children presenting with acute symptoms satisfying criteria for PANDAS/PANS.

Refractive outcomes of intraoperative wavefront aberrometry versus optical biometry alone for intraocular lens power calculation.

PURPOSE: To compare the outcomes of intraoperative wavefront aberrometry versus optical biometry alone for intraocular lens (IOL) power calculation in eyes undergoing cataract surgery with monofocal IOL implantation. METHODS: Preoperative data were obtained with the IOLMaster. Intraoperative aphakic measurements and IOL power calculations were obtained in some patients with the optiwave refractive analysis (ORA) system. Analysis was performed to determine the accuracy of monofocal IOL power prediction and postoperative manifest refraction at 1 month of the ORA versus IOLMaster. RESULTS: Two hundred and ninety-five eyes reviewed, 61 had only preoperative IOLMaster measurements and 234 had both IOLMaster and ORA measurements. Of these 234 eyes, 6 were excluded, 107 had the same recommended IOL power by ORA and IOLMaster. Sixty-four percent of these eyes were within ±0.5D. 95 eyes had IOL power implantation based on ORA instead of IOLMaster. Seventy percent of these eyes were within ±0.5D of target refraction. 26 eyes had IOL power chosen based on IOLMaster predictions instead of ORA. Sixty-five percent were within ±0.5D. In the group with IOLMaster without ORA measurements, 80% of eyes were within ±0.5D of target refraction. The absolute error was statistically smaller in those eyes where the ORA and IOLMaster recommended the same IOL power based on preoperative target refraction compared to instances in which IOL selection was based on ORA or IOLMaster alone. Neither prediction errors were statistically different between the ORA and IOLMaster alone. CONCLUSION: Intraoperative wavefront aberrometry with the ORA system provides postoperative refractive results comparable to conventional biometry with the IOLMaster for monofocal IOL selection.

Cerebrovascular Reactivity and Intellectual Outcome in Childhood Stroke With Transient Cerebral Arteriopathy.

BACKGROUND: Hypercapnic-challenge blood oxygen level-dependent magnetic resonance imaging cerebrovascular reactivity (CVR), measures the regional perfusion response to altered carbon dioxide. CVR correlates with the tissue-level microvascular dysfunction and ischemic risk. Among children with arterial ischemic stroke, transient cerebral arteriopathy (TCA) is a frequent, nonprogressive unilateral intracranial arteriopathy, which typically results in basal ganglia infarction and chronic cerebral artery stenosis. Therefore TCA provides a model for studying the consequences of chronic nonprogressive stenosis using CVR and intellectual outcome. We hypothesized that children with TCA and chronic nonprogressive intracranial artery stenosis have impaired CVR distal to the stenosis and associated cognitive impairment. METHODS: We studied children with a prior diagnosis of TCA as defined by infarction limited to the basal ganglia, internal capsule, or both; and significant (greater than 50% diameter) residual stenosis of the supraclinoid internal carotid artery, its proximal branches or both. All children had CVR, intellectual function, and infarct volumes quantified. RESULTS: We performed CVR studies in five children at mean 8.96 years (3.33 to 14.58 years) poststroke. Impaired CVR was limited to the infarct zone and adjacent white matter in most children. Intellectual function was broadly average in all but one subject. CONCLUSIONS: In children with typical TCA, ipsilateral cortical CVR and intellectual function seem to be preserved despite persistent arterial stenosis in the majority. These findings suggest that chronic revascularization strategies in these children may not be indicated and require further exploration in a larger cohort of children.

MRI in the evaluation of localization-related epilepsy.

This article covers the MRI evaluation of patients with epilepsy, with a focus on neuroimaging in those with localization-related epilepsy who may be potential epilepsy surgery candidates. The article includes structural MRI to identify a lesion, functional MRI to identify the eloquent cortex and diffusion tensor imaging to identify the eloquent white matter tracts. We consider the equipment, protocol or procedures, and reporting of MRI in patients with epilepsy. Recommendations for both adult and pediatric patients are described for protocols and procedures. The authors hope that this article will provide a standardized approach for clinical imaging of patients with suspected localization-related epilepsy who may be evaluated for epilepsy surgery. J. Magn. Reson. Imaging 2016.

Mediators of the Age Effect in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST).

BACKGROUND AND PURPOSE: There is higher combined risk of stroke or death (S+D) at older ages with carotid stenting. We assess whether this can be attributed to patient or arterial characteristics that are in the pathway between older age and higher risk. METHODS: Mediation analysis of selected patient (hypertension, diabetes mellitus, and dyslipidemia) and arterial characteristics assessed at the clinical sites and the core laboratory (plaque length, eccentric plaque, ulcerated plaque, percent stenosis, peak systolic velocity, and location) was performed in 1123 carotid artery stenting-treated patients in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST). We assessed the association of age with these characteristics, the association of these characteristics with stroke risk, and the amount of mediation of the association of age on the combined risk of periprocedural S+D with adjustment for these factors. RESULTS: Only plaque length as measured at the sites increased with age, was associated with increased S+D risk and significantly mediated the association of age on S+D risk. However, adjustment for plaque length attenuated the increased risk per 10 years of age from 1.72 (95% confidence interval, 1.26-2.37) to 1.66 (95% confidence interval, 1.20-2.29), accounting for only 8% of the increased risk. CONCLUSIONS: Plaque length seems to be in the pathway between older age and higher risk of S+D among carotid artery stenting-treated patients, but it mediated only 8% of the age effect excess risk of carotid artery stenting in CREST. Other factors and mechanisms underlying the age effect need to be identified as plaque length will not identify elderly patients for whom stenting is safe relative to endarterectomy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732.

Prevalence of inherited neurotransmitter disorders in patients with movement disorders and epilepsy: a retrospective cohort study.

BACKGROUND: Inherited neurotransmitter disorders are primary defects of neurotransmitter metabolism. The main purpose of this retrospective cohort study was to identify prevalence of inherited neurotransmitter disorders. METHODS: This retrospective cohort study does not have inclusion criteria; rather included all patients who underwent cerebrospinal fluid (CSF) homovanillic and 5-hydroxyindol acetic acid measurements. Patients with CSF neurotransmitter investigations suggestive of an inherited neurotransmitter disorder and patients with normal or non-diagnostic CSF neurotransmitter investigations underwent direct sequencing of single gene disorders. RESULTS: There were 154 patients between October 2004 and July 2013. Four patients were excluded due to their diagnosis prior to this study dates. Two major clinical feature categories of patients who underwent lumbar puncture were movement disorders or epilepsy in our institution. Twenty out of the 150 patients (13.3%) were diagnosed with a genetic disorder including inherited neurotransmitter disorders (6 patients) (dihydropteridine reductase, 6-pyruvoyl-tetrahydropterin synthase, guanosine triphosphate cyclohydrolase I, tyrosine hydroxylase, pyridoxine dependent epilepsy due to mutations in the ALDH7A1 gene and pyridoxamine-5-phosphate oxidase deficiencies) and non-neurotransmitter disorders (14 patients). CONCLUSION: Prevalence of inherited neurotransmitter disorders was 4% in our retrospective cohort study. Eight out of the 150 patients (5.3%) had one of the treatable inherited metabolic disorders with favorable short-term neurodevelopmental outcomes, highlighting the importance of an early and specific diagnosis. Whole exome or genome sequencing might shed light to unravel underlying genetic defects of new inherited neurotransmitter disorders in near future.

Continuous Electroencephalogram in Comatose Postcardiac Arrest Syndrome Patients Treated With Therapeutic Hypothermia: Outcome Prediction Study.

PURPOSE: Therapeutic Hypothermia (TH) is the only therapeutic intervention proven to significantly improve survival and neurologic outcome in comatose postcardiac arrest patients and is now considered standard of care. When we discuss prognostication with regard to comatose survivors postcardiac arrest, we should look for tools that are both reliable and accurate and that achieve a false-positive rate (FPR) equal to or very closely approaching zero. METHODS: We retrospectively reviewed data that were prospectively collected on all cardiac arrest patients admitted to our ICU. Continuous electroencephalogram (cEEG) monitoring was performed as part of our protocol for therapeutic hypothermia in comatose postcardiac arrest patients. The primary outcome measure was the best score on hospital discharge on the 5-point Glasgow-Pittsburgh cerebral performance category (CPC) scores. RESULTS: A total of 58 patients were included in this study. Twenty five (43%) patients had a good neurologic outcome (CPC score of 1-2). Three (5.2%) patients had nonconvulsive status epilepticus, all of whom had poor outcome (CPC = 5). Seventeen (29%) patients had burst suppression (BS); all had poor outcome. Both nonconvuslsive seizures (NCS) and BS had a specificity of 100% (95% confidence interval [CI], 84%-100%), positive predictive values of 100% (95% CI, 31%-100%), and 100% (95% CI, 77%-100%), respectively. Both NCS and BS had FPRs of zero (95% CI, 0.0-0.69, and 0.0-0.23, respectively). CONCLUSIONS: In comatose postcardiac arrest patients treated with hypothermia, EEG during the maintenance and rewarming phase of hypothermia can contribute to prediction of neurologic outcome. Pending large multicenter prospective studies evaluating the role of cEEG in prognostication, our study adds to the existing evidence that cEEG can play a potential role in prediction of outcome in postcardiac arrest patients treated with hypothermia.

An advanced course in long term care for geriatric medicine fellows.

Long term care deserves focused attention within a geriatric medicine fellowship curriculum to ensure that graduates are prepared not only for clinical care but also for the leadership, administrative, educational, quality improvement, and health policy aspects of their future roles. This report describes the curriculum development and program evaluation of an advanced course in long term care for geriatric medicine fellows and other graduate/post-graduate health professionals at Duke University. Course evaluation had 4 goals: (1) to determine how well the learning objectives were met; (2) to evaluate individual components of the course to improve subsequent offerings; (3) to determine whether additional topics needed to be added; and (4) to evaluate the effectiveness of the discussion forum component of the course. Learner self-efficacy improved within all competency areas but especially those of practice-based learning and system-based practice. Evaluation results led to curriculum revision that has maintained course relevance and sustained it within the larger geriatrics fellowship curriculum. Components of this course can be easily adapted to other curricular settings for fellows and residents.

Assessment of cerebrovascular reactivity using real-time BOLD fMRI in children with moyamoya disease: a pilot study.

PURPOSE: This pilot study aims to test the reliability and clinical validity of the assessment of cerebrovascular reactivity (CVR) with real-time blood-oxygen-level-dependent (BOLD) fMRI (rtCVR) in comparison with standard off-line processing in children with moyamoya disease. METHODS: Eight consecutive pediatric patients with moyamoya cerebral arteriopathy underwent BOLD fMRI CVR studies either on a 1.5-T or on a 3-T scanner with breath-holding techniques in six patients and under general anesthesia (GA) in three patients. One patient had undergone CVR study initially without and later with GA, and another had undergone CVR study before and after a revascularization procedure. The off-line and real-time processing of the data was done, and the results were compared for general quality and adequacy of the study (scale 0-3, 3 being the best) and for the presence or absence of abnormal reactivity and the location, pattern, and extent of abnormal reactivity. RESULTS: A total of 20 CVR series each was studied on real-time functional MRI and off-line analysis (eight patients, ten sessions, two series per session). All eight sessions done under GA were rated as quality class 3 (100 %), whereas only 5 of the 12 (41.7 %) studies with breath-holding technique were considered to be of best quality (class 3). In comparison to the off-line processing, the overall sensitivity of the rtCVR technique was 90 % with a specificity of 100 %. CONCLUSIONS: rtCVR assessment in children with moyamoya disease is feasible, and the results are comparable to that of standard off-line analysis. The results from off-line analysis are only available, at the earliest, several hours after the MRI has been completed. rtCVR can overcome this difficulty and may be equally reliable.

Cardiac transplantation in Friedreich ataxia.

In this article, we describe a 14-year-old boy with a confirmed diagnosis of Friedreich ataxia who underwent cardiac transplantation for left ventricular failure secondary to dilated cardiomyopathy with restrictive physiology. His neurological status prior to transplantation reflected early signs of neurological disease, with evidence of dysarthria, weakness, mild gait impairment, and limb ataxia. We review the ethical issues considered during the process leading to the decision to offer cardiac transplantation.

Toward a "smart" nightstand prototype: an examination of nightstand table contents and preferences.

OBJECTIVE: Two studies were conducted to obtain an understanding of the types of items seniors keep in their nightstands and to understand how users feel about the possibility of "smart" furniture. BACKGROUND: To enable aging in place and universal design, it is vital to understand the needs of a broad range of aging individuals, especially since there is little research on nightstand usage and design. METHODS: Study 1 allowed for the development of a structured inventory of nightstand use today in assisted living and rehabilitation facilities. Study 1 led to Study 2, demonstrating the need to conceptualize new ideas for smart nightstands. Feedback was obtained from intergenerational participants who could discuss their needs and preferences for a smart nightstand. RESULTS: In Study 1, more than 150 items were recorded and categorized into 25 different groups. The authors found that participants utilized the top portion of their nightstand as opposed to the lower sections; most items were found on top of the nightstand or in the top drawer. In Study 2, the authors found that the vast majority of participants are willing to consider the use of a smart nightstand. Participants discussed key functions and design preferences, which included carefully designed storage, the ability to move the nightstand up and down, contemporary design, and interaction through voice activation. CONCLUSION: Existing nightstands do not meet the needs of current users. This research provides greater understanding of the existing limitations associated with nightstands. Study 2 confirmed that user-centered design and the use of technology can be used to enhance daily living. Smart furniture may play a role in promoting the health and independence of diverse user groups.

Measurement of cerebrovascular reactivity in pediatric patients with cerebral vasculopathy using blood oxygen level-dependent MRI.

BACKGROUND AND PURPOSE: Cerebrovascular reactivity (CVR) is an indicator of cerebral hemodynamics. In adults with cerebrovascular disease, impaired CVR has been shown to be associated with an increased risk of stroke. In children, however, CVR studies are not common. This may be due to the difficulties and risks associated with current CVR study methodologies. We have previously described the application of precise control of end-tidal carbon dioxide partial pressure for CVR studies in adults. Our aim is to report initial observations of CVR studies that were performed as part of a larger observational study regarding investigations in pediatric patients with cerebral vascular disease. METHODS: Thirteen patients between the ages of 10 and 16 years (10 with a diagnosis of Moyamoya vasculopathy and 3 with confirmed, or suspected, intracranial vascular stenosis) underwent angiography, MRI, and functional blood oxygen level-dependent MRI mapping of CVR to hypercapnia. The results of the CVR study were then related to both the structural imaging and clinical status. RESULTS: Sixteen blood oxygen level-dependent MRI CVR studies were performed successfully in 13 consecutive patients. Twelve of the 13 patients with angiographic abnormalities also had CVR deficits in the corresponding downstream vascular territories. CVR deficits were also seen in 8 of 9 symptomatic patients and 2 of the asymptomatic patients. Notably, in patients with abnormalities on angiography, the reductions in CVR extended beyond the ischemic lesions identified with MR structural imaging into normal-appearing brain parenchyma. CONCLUSIONS: This is the first case series reporting blood oxygen level-dependent MRI CVR in children with cerebrovascular disease. CVR studies performed so far provide information regarding hemodynamic compromise, which complements traditional clinical assessment and structural imaging.

Physician knowledge, assessment, and reporting of older driver fitness.

ABSTRACT Physicians have the potential to serve as an important portal for information gathering, assessment, counseling, and reporting older driver fitness, as almost all older adults require medical care and have a primary care physician. However, there are few studies that have evaluated physician knowledge about, attitudes toward, and performance of older driver fitness assessment. Two pilot studies were conducted to assess physician knowledge and attitudes and aid understanding of physician knowledge of legal reporting requirements regarding older driver medical fitness. Results suggest that although physicians believe that patients should be evaluated for safe driving, many physicians do not routinely assess fitness to drive and few feel qualified to do so. It also appears that physicians may not be adequately knowledgeable about laws about reporting unsafe drivers. Thus, occupational therapy practitioners have an opportunity to educate about driving as a complex instrumental activity of daily living.

Simulator sickness during driving simulation studies.

While driving simulators are a valuable tool for assessing multiple dimensions of driving performance under relatively safe conditions, researchers and practitioners must be prepared for participants that suffer from simulator sickness. This paper describes multiple theories of motion sickness and presents a method for assessing and reacting to simulator sickness symptoms. Results showed that this method identified individuals who were unable to complete a driving simulator study due to simulator sickness with greater than 90% accuracy and that older participants had a greater likelihood of simulator sickness than younger participants. Possible explanations for increased symptoms experienced by older participants are discussed as well as implications for research ethics and simulator sickness prevention.

Pediatric constraint-induced movement therapy is associated with increased contralateral cortical activity on functional magnetic resonance imaging.

The mechanism behind constraint-induced movement therapy (constraint therapy) success is unknown. Study objectives were to evaluate cortical change after modified constraint therapy and explore a novel approach to quantify developmental disregard. Five participants underwent modified constraint therapy. Functional magnetic resonance imaging (MRI) and clinical measures were done pretreatment and posttreatment. Developmental disregard indices were calculated. Four participants showed clinical improvement posttreatment. Functional MRI laterality indices were variable pretreatment and exclusively contralateral among participants posttreatment. The disregard index range was -12.9 to 62.6 among participants. Disregard indices were correlated with change scores after treatment on the Pediatric Motor Activity Log amount of use domain (r = .93, P = .02), Assisting Hand Assessment (r = .93, P = .02), and grip strength (r = .92, P = .03). Study results suggest that a shift to or persistence of contralateral cortical activity for affected hand movement is important for constraint therapy mechanism of action; and developmental disregard may be a predictor of positive response to treatment.