Faculty Bibliography

Background: Sturge-Weber syndrome (SWS) involves the skin, brain, and eyes. The dermatologic manifestation is the facial port wine birthmark (PWB), while there are several potential neurologic and ophthalmologic manifestations, notably epilepsy and glaucoma, respectively. This consensus aims to develop evidence-based expert-defined recommendations for management of the neurologic and ophthalmic features and provides a framework for dermatologists to determine workup for patients with PWB who seek laser treatment. Study Design/Materials and Method: Thirteen national experts in neurology, radiology, and ophthalmology were assembled as part of a larger consensus statement for the management of SWS. Key topics and questions regarding risk stratification, referral indications, and treatment were formulated. A systematic PubMed search was performed. Evidence-based recommendations were developed.
Result(s): High-risk PWB distributions involve the hemifacial, forehead, or median locations, including the upper eyelids, especially when concerned for glaucoma. Any child with a high-risk facial PWB should be referred to a pediatric neurologist and pediatric ophthalmologist for a baseline evaluation, with periodic follow-up. Routine screening for brain involvement is not recommended for newborns and infants with a high-risk PWB and no history of seizures or neurological symptoms but can be performed in cases of extreme parental anxiety, an abnormal EEG, or when presymptomatic treatment is contemplated such as with extensive bilateral PWB. In children with stable neurocognitive symptoms, routine follow-up neuroimaging is not advised. In adults with a high-risk PWB and no prior imaging, neuroimaging should be obtained, but follow-up neuroimaging is not recommended in adults with established SWS and stable neurocognitive symptoms. The treatment of glaucoma varies depending on the patient's age and clinical presentation.
Conclusion(s): Recommendations were developed by experts in neurology, neuroradiology, and ophthalmology. These guidelines can guide evidence-based discussions between patients and providers and increase dermatologists' awareness regarding when and what workup is necessary in patients seeking laser treatment for PWB

The International League Against Epilepsy (ILAE) seizure classification scheme has been periodically updated to improve its reliability and applicability to clinicians and researchers alike. Here, members of the Epilepsy Study Consortium propose a pragmatic seizure classification, based on the ILAE scheme, designed for use in clinical trials with a focus on outcome measures that have high reliability, broad interpretability across stakeholders, and clinical relevance in the context of the development of novel antiseizure medications. Controversies around the current ILAE classification scheme are discussed in the context of clinical trials, and pragmatic simplifications to the existing scheme are proposed, for intended use by investigators, industry sponsors, and regulatory agencies.

PURPOSE/OBJECTIVE:Gait improvement following high-volume lumbar puncture (HVLP) and continuous lumbar drain (cLD) is widely used to predict shunt response in patients with suspected normal pressure hydrocephalus (NPH). Here, we investigate differences in MRI volumetric and traditional measures between HVLP/cLD responders and non-responders to identify imaging features that may help predict HVLP/cLD response. METHODS:Eighty-two patients with suspected NPH were studied retrospectively. Gait testing was performed before and immediately/24 h/72 h after HVLP/cLD. A positive response was defined as improvement in gait post-procedure. Thirty-six responders (26 men; mean age 79.3 ± 6.3) and 46 non-responders (25 men; mean age 77.2 ± 6.1) underwent pre-procedure brain MRI including a 3D T1-weighted sequence. Subcortical regional volumes were segmented using FreeSurfer. After normalizing for total intracranial volume, two-way type III ANCOVA test and chi-square test were used to characterize statistical group differences. Evans' index, callosal angle (CA), and disproportionately enlarged subarachnoid space hydrocephalus were assessed. Multivariable logistic regression models were tested using Akaike information criterion to determine which combination of metrics most accurately predicts HVLP/cLD response. RESULTS:Responders and non-responders demonstrated no differences in total ventricular and white/gray matter volumes. CA (men only) and third and fourth ventricular volumes were smaller; and hippocampal volume was larger in responders (p < 0.05). Temporal horns volume correlated with degree of improvement in gait velocity in responders (p = 0.0006). The regression model was 76.8% accurate for HVLP/cLD response. CONCLUSION/CONCLUSIONS:CA and third and fourth ventricular volumes and hippocampal volume may serve as potentially useful imaging features that may help predict spinal tap response and hence potentially shunt response.

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.

The dominant paradigm in turbulent wall flows is that the mean velocity near the wall, when scaled on wall variables, is independent of the friction Reynolds number. This paradigm faces challenges when applied to fluctuations but has received serious attention only recently. Here, by extending our earlier work (Chen & Sreenivasan, J. Fluid Mech., vol. 908, 2021, p. R3) we present a promising perspective, and support it with data, that fluctuations displaying non-zero wall values, or near-wall peaks, are bounded for large values of, owing to the natural constraint that the dissipation rate is bounded. Specifically, where represents the maximum value of any of the following quantities: energy dissipation rate, turbulent diffusion, fluctuations of pressure, streamwise and spanwise velocities, squares of vorticity components, and the wall values of pressure and shear stresses; the subscript denotes the bounded asymptotic value of, and the coefficient depends on but not on. Moreover, there exists a scaling law for the maximum value in the wall-normal direction of high-order moments, of the form, where represents the streamwise or spanwise velocity fluctuation, and and are independent of. Excellent agreement with available data is observed. A stochastic process for which the random variable has the form just mentioned, referred to here as the 'linear -norm Gaussian', is proposed to explain the observed linear dependence of on.

Despite increased neuroscience interest at the undergraduate level, a significant shortage of neurologists in the United States (US) exists. To better understand how to generate more interest in neurology specifically at the undergraduate level, we conducted an anonymous cross-sectional online survey of 1085 undergraduates either in neuroscience courses or majoring/minoring in neuroscience from across the US to better understand their clinical neurology experiences and perspectives. The survey quantitatively and qualitatively assessed students' clinical neurology exposure inside and outside of the classroom, research experiences and career goals. Students were from a broad spectrum of undergraduate institutions (public research university (40.8%), liberal arts College (29.7%) and private research university (29.0%). Most students (89.9%) were looking to pursue graduate studies; 56.9% reported wanting to be a physician and 17.8% expressed interest in obtaining an MD/PhD. Importantly, students reported first exposure to neuroscience at age 16 but felt that they could be exposed to neuroscience as early as 13. Half (50.5%) decided to major in neuroscience before college and a quarter (25.6%) decided to major in their first year of college. Despite high interest in clinical neurology exposure, less than one-third of students had spoken with or shadowed a neurologist, and only 13.6% had interacted with clinical neurology populations. Only 20.8% of students felt volunteer and internship opportunities were sufficiently available. Qualitative results include student perspectives from those who did and did not work with a neurologist, describing how they were or were not able to obtain such opportunities. We discuss translating the survey findings into actionable results with opportunities to target the undergraduate neuroscience interest to improve the neurology pipeline. We describe existing programs that could be integrated into everyday neurology practices and new approaches to learning and training to help leverage the significant undergraduate neuroscience interest. We also raise questions for further research, including exploring (1) how students learn of neurologic conditions/expand their knowledge about additional neurologic conditions, (2) whether qualitative investigation of the experiences of neuroscience undergraduates at specific institutions might provide additional insight, and (3) systems to maintain interest in neuroscience/neurology as students enter medical school.

Importance:Current guidelines recommend against use of intravenous alteplase in patients with acute ischemic stroke who are taking non-vitamin K antagonist oral anticoagulants (NOACs). Objective:To evaluate the safety and functional outcomes of intravenous alteplase among patients who were taking NOACs prior to stroke and compare outcomes with patients who were not taking long-term anticoagulants. Design, Setting, and Participants:A retrospective cohort study of 163 038 patients with acute ischemic stroke either taking NOACs or not taking anticoagulants prior to stroke and treated with intravenous alteplase within 4.5 hours of symptom onset at 1752 US hospitals participating in the Get With The Guidelines-Stroke program between April 2015 and March 2020, with complementary data from the Addressing Real-world Anticoagulant Management Issues in Stroke registry. Exposures:Prestroke treatment with NOACs within 7 days prior to alteplase treatment. Main Outcomes and Measures:The primary outcome was symptomatic intracranial hemorrhage occurring within 36 hours after intravenous alteplase administration. There were 4 secondary safety outcomes, including inpatient mortality, and 7 secondary functional outcomes assessed at hospital discharge, including the proportion of patients discharged home. Results:Of 163 038 patients treated with intravenous alteplase (median age, 70 [IQR, 59 to 81] years; 49.1% women), 2207 (1.4%) were taking NOACs and 160 831 (98.6%) were not taking anticoagulants prior to their stroke. Patients taking NOACs were older (median age, 75 [IQR, 64 to 82] years vs 70 [IQR, 58 to 81] years for those not taking anticoagulants), had a higher prevalence of cardiovascular comorbidities, and experienced more severe strokes (median National Institutes of Health Stroke Scale score, 10 [IQR, 5 to 17] vs 7 [IQR, 4 to 14]) (all standardized differences >10). The unadjusted rate of symptomatic intracranial hemorrhage was 3.7% (95% CI, 2.9% to 4.5%) for patients taking NOACs vs 3.2% (95% CI, 3.1% to 3.3%) for patients not taking anticoagulants. After adjusting for baseline clinical factors, the risk of symptomatic intracranial hemorrhage was not significantly different between groups (adjusted odds ratio [OR], 0.88 [95% CI, 0.70 to 1.10]; adjusted risk difference [RD], -0.51% [95% CI, -1.36% to 0.34%]). There were no significant differences in the secondary safety outcomes, including inpatient mortality (6.3% for patients taking NOACs vs 4.9% for patients not taking anticoagulants; adjusted OR, 0.84 [95% CI, 0.69 to 1.01]; adjusted RD, -1.20% [95% CI, -2.39% to -0%]). Of the secondary functional outcomes, 4 of 7 showed significant differences in favor of the NOAC group after adjustment, including the proportion of patients discharged home (45.9% vs 53.6% for patients not taking anticoagulants; adjusted OR, 1.17 [95% CI, 1.06 to 1.29]; adjusted RD, 3.84% [95% CI, 1.46% to 6.22%]). Conclusions and Relevance:Among patients with acute ischemic stroke treated with intravenous alteplase, use of NOACs within the preceding 7 days, compared with no use of anticoagulants, was not associated with a significantly increased risk of intracranial hemorrhage.

INTRODUCTION/UNASSIGNED:Little is known about chaplains' views on brain death/death by neurologic criteria (BD/DNC). Thematic analysis of comments made by hospital chaplains about BD/DNC can illuminate their perspectives on working with patients, families, and interdisciplinary teams during assessment for BD/DNC. MATERIALS AND METHODS/UNASSIGNED:In an electronic survey distributed to members of five chaplaincy organizations between February and July 2019, we elicited free-text comments about BD/DNC. We performed a thematic analysis of the comments. RESULTS/UNASSIGNED:Four themes were present: (1) definition of life and death, (2) respect with a subtheme of physician obligation, (3) collaboration with a subtheme of communication, and (4) education with a subtheme of scepticism. CONCLUSIONS/UNASSIGNED:Hospital chaplains are essential members of the interdisciplinary team involved in BD/DNC evaluation. They aim to ensure the interaction between families and the interdisciplinary team at the boundary of life and death and the intersection between religion and medicine is respectful, collaborative, and educational.

Ambiguous images elicit bistable perception, wherein periods of momentary perceptual stability are interrupted by sudden perceptual switches. When intermittently presented, ambiguous images trigger a perceptual memory trace in the intervening blank periods. Understanding the neural bases of perceptual stability and perceptual memory during bistable perception may hold clues for explaining the apparent stability of visual experience in the natural world, where ambiguous and fleeting images are prevalent. Motivated by recent work showing the involvement of the right inferior frontal gyrus (rIFG) in bistable perception, we conducted a transcranial direct-current stimulation (tDCS) study with a double-blind, within-subject cross-over design to test a potential causal role of rIFG in these processes. Subjects viewed ambiguous images presented continuously or intermittently while under EEG recording. We did not find any significant tDCS effect on perceptual behavior. However, the fluctuations of oscillatory power in the alpha and beta bands predicted perceptual stability, with higher power corresponding to longer percept durations. In addition, higher alpha and beta power predicted enhanced perceptual memory during intermittent viewing. These results reveal a unified neurophysiological mechanism sustaining perceptual stability and perceptual memory when the visual system is faced with ambiguous input.