Faculty Bibliography

INTRODUCTION/BACKGROUND:Many patients admitted to hospitals with acute trauma have positive serum blood alcohol levels. Published associations between alcohol use, injury patterns, and outcomes are inconsistent. We sought to further delineate the impact of alcohol use and alcohol withdrawal on hospital outcomes amongst acute trauma patients. METHODS:We performed a retrospective analysis of adult trauma patients hospitalized at a suburban level 1 trauma center between January 2015 and September 2019 with a blood alcohol level measurement and/or classification as alcohol withdrawal syndrome (AWS). Patients were separated into three groups: BAL ≤10 mg/dL, BAL >10 mg/dL, and alcohol withdrawal syndrome (AWS). RESULTS:Overall, 3896 patients met study criteria with 75.6% BAL ≤10, 23.2% BAL >10, and 1.2% AWS. The median age was significantly different (BAL ≤ 10: 59 years, BAL > 10: 44 years, AWS: 53.5 years). Alcohol withdrawal was experienced by patients with BAL ≤10 and BAL >10. While injury severity and mortality were similar across all 3 groups, AWS patients experienced significantly longer hospital and ICU lengths of stay, unplanned ICU admission, need for mechanical ventilation, and higher rates of complications. Patients with AWS had high rates of acute neuropsychiatric symptoms, complicating their management. CONCLUSIONS:Except for mortality, AWS patients experienced worse outcomes. The complex nature of alcohol withdrawal cases, including the possibility of developing AWS despite a negative BAL on admission, emphasizes the need for early assessment for alcohol withdrawal risk factors and input from specialists.

Axial disorders, including postural deformities, postural instability, and gait disturbances, are among the most disabling symptoms of Parkinson's disease (PD). Equistasi®, a wearable proprioceptive stabilizer device, has been proposed as neurological rehabilitative device for this set of symptoms. To investigate the effects of the device on gait and balance, 24 participants affected by PD were enrolled in this crossover double-dummy, randomized, controlled study. Subjects were assessed four times before and after 8 weeks treatment with either active or placebo device; one-month wash-out was taken between treatments, in a 20-week timeframe. Gait analysis and instrumented Romberg test were performed with the aid of a sterofotogrammetric system and two force plates. Joint kinematics, spatiotemporal parameters of gait and center of pressure parameters were extracted. Paired T-test (p < 0.05) was adopted after evidence of normality to compare the variables across different acquisition sessions; Wilcoxon was adopted for non-normal distributions. Before and after the treatment with the active device, statistically significant improvements were observed in trunk flexion extension and in the ankle dorsi-plantarflexion. Regarding balance assessment, significant improvements were reported at the frequencies corresponding to vestibular system. These findings may open new possibilities on PD's rehabilitative interventions. Research question, tailored design of the study, experimental acquisition overview, main findings, and conclusions.

BACKGROUND:Elevated systolic blood pressure (SBP) in the acute phase after endovascular therapy (EVT) is associated with worse outcome. However, the association between systolic blood pressure reduction (SBPr) and the outcome of EVT is not well understood. OBJECTIVE:To determine the association between SBPr and clinical outcomes after EVT in a prospective multicenter cohort. METHODS:A post hoc analysis of the Blood Pressure after Endovascular Stroke Therapy (BEST) prospective observational cohort study was carried out. SBPr was defined as the absolute difference between admission SBP and mean SBP in the first 24 hours after EVT. Logistic regression was used to assess the association between SBPr and poor functional outcome (modified Rankin Scale score 3-6) at 90 days. RESULTS:A total of 259/433 (58.5%) patients had poor outcome. SBPr was higher in the poor outcome group than in the good outcome group (26.6±27.4 vs 19.0±22.3 mm Hg; p<0.001). However, in adjusted models, SBPr was not independently associated with poor outcome (OR=1.00 per 1 mm Hg increase, 95% CI 0.99 to 1.01) or death (OR=0.9 per 1 mm Hg increase; 95% CI 0.98 to 1.00). No association remained when SBPr was divided into tertiles. Subgroup analyses based on history of hypertension, revascularization status, and antihypertensive treatment yielded similar results. CONCLUSION/CONCLUSIONS:The reduction in baseline SBP following EVT was not associated with poor functional outcomes. Most of the cohort (88%) achieved successful recanalization, and therefore, these results mainly apply to patients with successful recanalization.

Angiogenesis is a central feature of glioblastoma (GBM), with contribution from several mechanisms and signaling pathways to produce an irregular, poorly constructed, and poorly connected tumor vasculature. Targeting angiogenesis has been efficacious for disease control in other cancers, and given the (I) highly vascularized environment in GBM and (II) correlation between glioma grade and prognosis, angiogenesis became a prime target of therapy in GBM as well. Here, we discuss the therapies developed to target these pathways including vascular endothelial growth factor (VEGF) signaling, mechanisms of tumor resistance to these drugs in the context of disease progression, and the evolving role of anti-angiogenic therapy in GBM.

PURPOSE/UNASSIGNED:To address the gap in the literature and clarify the expanding role of wearable sensor data in stroke rehabilitation, we summarized the methods for upper extremity (UE) sensor-based assessment and sensor-based treatment. MATERIALS AND METHODS/UNASSIGNED:The guideline outlined by the preferred reporting items for systematic reviews and meta-analysis extension for scoping reviews was used to complete this scoping review. Information pertaining to participant demographics, sensory information, data collection, data processing, data analysis, and study results were extracted from the studies for analysis and synthesis. RESULTS/UNASSIGNED:We included 43 articles in the final review. We organized the results into assessment and treatment categories. The included articles used wearable sensors to identify UE functional motion, categorize motor impairment/activity limitation, and quantify real-world use. Wearable sensors were also used to augment UE training by triggering sensory cues or providing instructional feedback about the affected UE. CONCLUSIONS/UNASSIGNED:Sensors have the potential to greatly expand assessment and treatment beyond traditional clinic-based approaches. This capability could support the quantification of rehabilitation dose, the nuanced assessment of impairment and activity limitation, the characterization of daily UE use patterns in real-world settings, and augment UE training adherence for home-based rehabilitation.IMPLICATIONS FOR REHABILITATIONSensor data have been used to assess UE functional motion, motor impairment/activity limitation, and real-world use.Sensor-assisted treatment approaches are emerging, and may be a promising tool to augment UE adherence in home-based rehabilitation.Wearable sensors may extend our ability to objectively assess UE motion beyond supervised clinical settings, and into home and community settings.

Background Intravenous alteplase improves outcome after acute ischemic stroke without a benefit in 90-day mortality. There are limited data on whether alteplase is associated with reduced mortality in patients with atrial fibrillation (AF)-related ischemic stroke whose mortality rate is relatively high. We sought to determine the association of alteplase with hemorrhagic transformation and mortality in patients with AF. Methods and Results We retrospectively analyzed consecutive patients with acute ischemic stroke between 2015 and 2018 diagnosed with AF included in the IAC (Initiation of Anticoagulation After Cardioembolic Stroke) study, which pooled data from stroke registries at 8 comprehensive stroke centers across the United States. For our primary analysis, we included patients who did not undergo mechanical thrombectomy (MT), and secondary analyses included patients who underwent MT. We used binary logistic regression to determine whether alteplase use was associated with risk of hemorrhagic transformation and 90-day mortality. There were 1889 patients (90.6%) who had 90-day follow-up data available for analyses and were included; 1367 patients (72.4%) did not receive MT, and 522 patients (27.6%) received MT. In our primary analyses we found that alteplase use was independently associated with an increased risk for hemorrhagic transformation (odds ratio [OR], 2.23; 95% CI, 1.57-3.17) but reduced risk of 90-day mortality (OR, 0.58; 95% CI, 0.39-0.87). Among patients undergoing MT, alteplase use was not associated with a significant reduction in 90-day mortality (OR, 0.68; 95% CI, 0.45-1.04). Conclusions Alteplase reduced 90-day mortality of patients with acute ischemic stroke with AF not undergoing MT. Further study is required to assess the efficacy of alteplase in patients with AF undergoing MT.

Neocortical heterotopia consist of ectopic neuronal clusters that are frequently found in individuals with cognitive disability and epilepsy. However, their pathogenesis remains poorly understood due in part to a lack of tractable animal models. We have developed an inducible model of focal cortical heterotopia that enables their precise spatiotemporal control and high-resolution optical imaging in live mice. Here, we report that heterotopia are associated with striking patterns of circumferentially projecting axons and increased myelination around neuronal clusters. Despite their aberrant axonal patterns, in vivo calcium imaging revealed that heterotopic neurons remain functionally connected to other brain regions, highlighting their potential to influence global neural networks. These aberrant patterns only form when heterotopia are induced during a critical embryonic temporal window, but not in early postnatal development. Our model provides a new way to investigate heterotopia formation in vivo and reveals features suggesting the existence of developmentally modulated, neuron-derived axon guidance and myelination factors.

Depression is associated with adverse outcomes in epilepsy but is undertreated in this population. Project UPLIFT, a telephone-based depression self-management program, was developed for adults with epilepsy and has been shown to reduce depressive symptoms in English-speaking patients. There remains an unmet need for accessible mental health programs for Hispanic adults with epilepsy. The purpose of this study was to evaluate the feasibility, acceptability, and effects on depressive symptoms of a culturally adapted version of UPLIFT for the Hispanic community. Hispanic patients with elevated depressive symptoms (n = 72) were enrolled from epilepsy clinics in New York City and randomized to UPLIFT or usual care. UPLIFT was delivered in English or Spanish to small groups in eight weekly telephone sessions. Feasibility was assessed by recruitment, retention, and adherence rates and acceptability was assessed by self-reported satisfaction with the intervention. Depressive symptoms (PHQ-9 scores) were compared between study arms over 12 months. The mean age was 43.3±11.3, 71% of participants were female and 67% were primary Spanish speakers. Recruitment (76% consent rate) and retention rates (86-93%) were high. UPLIFT participants completed a median of six out of eight sessions and satisfaction ratings were high, but rates of long-term practice were low. Rates of clinically significant depressive symptoms (PHQ-9 ≥5) were lower in UPLIFT versus usual care throughout follow-up (63% vs. 72%, 8 weeks; 40% vs. 70%, 6 months; 47% vs. 70%, 12 months). Multivariable-adjusted regressions demonstrated statistically significant differences at 6 months (OR = 0.24, 95% CI, 0.06-0.93), which were slightly reduced at 12 months (OR = 0.30, 95% CI, 0.08-1.16). Results suggest that UPLIFT is feasible and acceptable among Hispanic adults with epilepsy and demonstrate promising effects on depressive symptoms. Larger trials in geographically diverse samples are warranted.

OBJECTIVE:To investigate the association of psychiatric and cognitive comorbidities with persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (TBI). METHODS:A total of 100 patients with persistent PTH attributed to mild TBI and 100 age- and gender-matched healthy controls free of mild TBI were enrolled between July 2018 and June 2019. Quality of sleep was evaluated using the Pittsburgh Sleep Quality Index, while symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Cognitive impairment was evaluated using the Montreal Cognitive Assessment questionnaire, while post-traumatic stress disorder (PTSD) was assessed using the Harvard Trauma Questionnaire. RESULTS:In 100 patients with persistent PTH, 85% reported poor quality sleep, compared with 42% of healthy controls (P < 0.01). The relative frequency of probable to high risk of anxiety was 52% in the persistent PTH group vs. 8% in healthy controls (P < 0.01), while the relative frequency of probable to high risk of depression was 42% in the persistent PTH group vs. 2% in healthy controls (P < 0.01). Furthermore, 27% of the patients with persistent PTH had mild cognitive impairment while 10% had probable PTSD. CONCLUSIONS:Poor quality of sleep as well as symptoms suggestive of anxiety and depression were more common in patients with persistent PTH than healthy controls. Clinicians should screen patients with persistent PTH for these comorbidities and develop treatment plans that account for their presence.

In the spring of 2021, reports of rare and unusual venous thrombosis in association with the ChAdOx1 and Ad26.COV2.S adenovirus-based coronavirus vaccines led to a brief suspension of their use by several countries. Thromboses in the cerebral and splanchnic veins among patients vaccinated in the preceding 4 weeks were described in 17 patients out of 7.98 million recipients of the Ad26.COV2.S vaccine (with 3 fatalities related to cerebral vein thrombosis) and 169 cases of cerebral vein thrombosis among 35 million ChAdOx1 recipients. Events were associated with thrombocytopenia and anti-PF4 (antibodies directed against platelet factor 4), leading to the designation vaccine-induced immune thrombotic thrombocytopenia. Unlike the related heparin-induced thrombotic thrombocytopenia, with an estimated incidence of <1:1000 patients treated with heparin, and a mortality rate of 25%, vaccine-induced immune thrombotic thrombocytopenia has been reported in 1:150 000 ChAdOx1 recipients and 1:470 000 Ad26.COV.2 recipients, with a reported mortality rate of 20% to 30%. Early recognition of this complication should prompt testing for anti-PF4 antibodies and acute treatment targeting the autoimmune and prothrombotic processes. Intravenous immunoglobulin (1 g/kg for 2 days), consideration of plasma exchange, and nonheparin anticoagulation (argatroban, fondaparinux) are recommended. In cases of cerebral vein thrombosis, one should monitor for and treat the known complications of venous congestion as they would in patients without vaccine-induced immune thrombotic thrombocytopenia. Now that the Ad26.COV2.S has been reapproved for use in several countries, it remains a critical component of our pharmacological armamentarium in stopping the spread of the human coronavirus and should be strongly recommended to patients. At this time, the patient and community-level benefits of these two adenoviral vaccines vastly outweigh the rare but serious risks of vaccination. Due to the relatively low risk of severe coronavirus disease 2019 (COVID-19) in young women (<50 years), it is reasonable to recommend an alternative vaccine if one is available. Ongoing postmarketing observational studies are important for tracking new vaccine-induced immune thrombotic thrombocytopenia cases and other rare side effects of these emergent interventions.