Faculty Bibliography

Despite the severity of coronavirus disease 2019 (COVID-19) being more frequently related to acute respiratory distress syndrome and acute cardiac and renal injuries, thromboembolic events have been increasingly reported. We report a unique series of young patients with COVID-19 presenting with cerebral venous system thrombosis. Three patients younger than 41 years of age with confirmed Severe Acute Respiratory Syndrome coronavirus 2 (SARS-Cov-2) infection had neurologic findings related to cerebral venous thrombosis. They were admitted during the short period of 10 days between March and April 2020 and were managed in an academic institution in a large city. One patient had thrombosis in both the superficial and deep systems; another had involvement of the straight sinus, vein of Galen, and internal cerebral veins; and a third patient had thrombosis of the deep medullary veins. Two patients presented with hemorrhagic venous infarcts. The median time from COVID-19 symptoms to a thrombotic event was 7 days (range, 2-7 days). One patient was diagnosed with new-onset diabetic ketoacidosis, and another one used oral contraceptive pills. Two patients were managed with both hydroxychloroquine and azithromycin; one was treated with lopinavir-ritonavir. All patients had a fatal outcome. Severe and potentially fatal deep cerebral thrombosis may complicate the initial clinical presentation of COVID-19. We urge awareness of this atypical manifestation.

Purpose/UNASSIGNED:The aim of this study was to test the discomfort experienced during intravitreal injections with eyelid retraction between an eyelid speculum, cotton-tipped applicator (CTA), and unimanual eyelid retraction techniques. Methods/UNASSIGNED:In total, 99 patients receiving intravitreal bevacizumab were enrolled into this prospective study. Participants were randomized to one of the three methods, given subconjunctival 2% lidocaine and then injected in the superior temporal quadrant. Immediately after the procedure, each patient was given a visual analog scale (VAS) to rate their discomfort. Results/UNASSIGNED:The mean pain scores for eyelid retraction with unimanual, CTA, and speculum groups were 0.788 (standard deviation [SD] 0.70, 95% confidence interval [CI] 0.448-1.128), 0.945 (SD 1.28, 95% CI 0.600-1.291), and 1.561 (SD 1.28, 95% CI 1.210-1.912), respectively. A one-way analysis of variance (ANOVA) test revealed a significant difference between the groups (P = 0.006). Post hoc analysis also revealed a difference in mean pain scores between the speculum and both the CTA and the unimanual methods. Conclusion/UNASSIGNED:Our study shows that the unimanual and CTA methods for eyelid retraction are significantly less painful for patients compared to the speculum method. Patient comfort is of the utmost importance as intravitreal injections are performed millions of times a year with most patients requiring multiple injections.

Patients, clinicians, and hospitals have undergone monumental changes during the COVID-19 pandemic. This time of troubles has forced us to consider the fundamental obligations that neurologists have to our own individual patients as well as the greater community. By returning to our fundamental understanding of these duties we can ensure that we are providing the most ethically appropriate contingency and crisis care possible. We recommend specific adaptations to both the inpatient and outpatient settings, as well as changes to medical and trainee education. Furthermore, we explore the daunting but potentially necessary implementation of scare resource allocation protocols. As the pandemic evolves, we will need to adapt continuously to these rapidly changing circumstances and consider both national and regional standards and variation.

BACKGROUND:In Parkinson's disease (PD), impulsive-compulsive behaviors (ICBs) may develop as side-effect of dopaminergic medications. Abnormal incentive-driven decision-making, which is supported by the cognitive control and motivation interaction, may represent an ICBs signature. This systematic review explored whether structural and/or functional brain differences between PD patients with vs without ICBs encompass incentive-driven decision-making networks. METHODS:Structural and functional neuroimaging studies comparing PD patients with and without ICBs, either de novo or medicated, were included. RESULTS:Thirty articles were identified. No consistent evidence of structural alteration both in de novo and medicated PD patients were found. Differences in connectivity within the default mode, the salience and the central executive networks predate ICBs development and remain stable once ICBs are fully developed. Medicated PD patients with ICBs show increased metabolism and cerebral blood flow in orbitofrontal and cingulate cortices, ventral striatum, amygdala, insula, temporal and supramarginal gyri. Abnormal ventral striatum connectivity with anterior cingulate cortex and limbic structures was reported in PD patients with ICBs. DISCUSSION/CONCLUSIONS:Functional brain signatures of ICBs in PD encompass areas involved in cognitive control and motivational encoding networks of the incentive-driven decision-making. Functional alterations predating ICBs may be related to abnormal synaptic plasticity in these networks.

OBJECTIVE:Understanding barriers and facilitators to engaging with implementation science (IS) research can provide insight into how to improve efforts to encourage more researchers to participate in IS research. STUDY DESIGN/METHODS:The study design used is a grounded theory qualitative study. METHODS:We conducted semistructured telephone interviews with 20 health researchers familiar with IS that both report engaging in IS research and those that do not. We explored perceptions of barriers and facilitators to engaging in IS research. Themes surrounding difficulties defining IS, lack of training availability, and obstacles to forming research partnerships were discussed as barriers to engaging IS research. Interview topics were informed by the result of an online survey of health researchers in the US. RESULTS:Themes surrounding difficulties defining IS, lack of training availability, and obstacles to forming research partnerships were discussed as barriers to engaging IS research. While accessible mentorship, exposure to formative experiences that develop interest in IS research and an increasing IS visibility were described as motivators for engaging in IS research. CONCLUSIONS:These results highlight the importance of mentorship and exposure to IS ideas in motivating engagement in IS research and the presence of training and methodological barriers to engagement. Future research should expand this line of inquiry to include the perspectives of more junior researchers and students to better reflect the current IS environment.

The paranodal junctions flank mature nodes of Ranvier and provide a barrier between ion channels at the nodes and juxtaparanodes. These junctions also promote node assembly and maintenance by mechanisms that are poorly understood. Here, we examine their role in the accumulation of NF186, a key adhesion molecule of PNS and CNS nodes. We previously showed NF186 is initially targeted/accumulates via its ectodomain to forming PNS (hemi)nodes by diffusion trapping whereas it is later targeted to mature nodes by a transport-dependent mechanism mediated by its cytoplasmic segment. To address the role of the paranodes in this switch, we compared accumulation of NF186 ectodomain and cytoplasmic domain constructs in wild type vs. paranode defective, i.e. Caspr-null mice. Both pathways are affected in the paranodal mutants. In the PNS of Caspr-null mice, diffusion trapping mediated by the NF186 ectodomain aberrantly persists into adulthood whereas the cytoplasmic domain/transport-dependent targeting is impaired. In contrast, accumulation of NF186 at CNS nodes does not undergo a switch - it is predominantly targeted to both forming and mature CNS nodes via its cytoplasmic domain and requires intact paranodes. FRAP analysis indicates the paranodes provide a membrane diffusion barrier that normally precludes diffusion of NF186 to nodes. Linkage of paranodal proteins to the underlying cytoskeleton likely contributes to this diffusion barrier based on 4.1B and βII spectrin expression in Caspr-null mice. Together, these results implicate the paranodes as membrane diffusion barriers that regulate targeting to nodes and highlight differences in the assembly of PNS and CNS nodes.SIGNIFICANCE STATEMENTNodes of Ranvier are essential for effective saltatory conduction along myelinated axons. A major question is how the various axonal proteins that comprise the multimeric nodal complex accumulate at this site. Here we examine how targeting of NF186, a key nodal adhesion molecule, is regulated by the flanking paranodal junctions. We show the transition from diffusion-trapping to transport-dependent accumulation of NF186 requires the paranodal junctions. We also demonstrate that these junctions are a barrier to diffusion of axonal proteins into the node and highlight differences in PNS and CNS node assembly. These results provide new insights into the mechanism of node assembly and the pathophysiology of neurological disorders in which impaired paranodal function contributes to clinical disability.

OBJECTIVE:To identify similarities and differences in protocols on determination of brain death/death by neurologic criteria (BD/DNC) around the world. METHODS:We collected and reviewed official national BD/DNC protocols from contacts around the world between January 2018 and April 2019. RESULTS:We communicated with contacts in 136 countries and found that 83 (61% of countries with contacts identified, 42% of the world) had BD/DNC protocols, 78 of which were unique. Protocols addressed the following prerequisites and provided differing instructions: drug clearance (64, 82%), temperature (61, 78%), laboratory values (56, 72%), observation period (37, 47%), and blood pressure (34, 44%). Protocols did not consistently identify the same components for the clinical examination of brain death; 70 (90%) included coma, 70 (90%) included the pupillary reflex, 68 (87%) included the corneal reflex, 67 (86%) included the oculovestibular reflex, 64 (82%) included the gag reflex, 62 (79%) included the cough reflex, 58 (74%) included the oculocephalic reflex, 37 (47%) included noxious stimulation to the face, and 22 (28%) included noxious stimulation to the limbs. Apnea testing was mentioned in 71 (91%) protocols; there was variability in the technique and target across protocols. Ancillary testing was included as a requirement for all determinations of BD/DNC in 22 (28%) protocols. CONCLUSIONS:There is considerable variability in BD/DNC determination protocols around the world. Medical standards for death should be the same everywhere. We recommend that a worldwide consensus be reached on the minimum standards for BD/DNC.

OBJECTIVE:To investigate the role of calcitonin gene-related peptide (CGRP) in persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (TBI). METHODS:A total of 100 individuals with persistent PTH attributed to mild TBI and 100 age- and gender-matched healthy controls were enrolled between July 2018 and June 2019. Blood was drawn from the antecubital vein and subsequently analyzed using a validated radioimmunoassay for human CGRP. Measurements were performed on coded samples by a board-certified laboratory technician who was blind to clinical information. RESULTS: = 0.85). CONCLUSIONS:CGRP plasma measurements are unlikely a feasible blood-based biomarker of persistent PTH. Future studies should assess whether CGRP plasma measurements can be used to predict development of persistent PTH.