Faculty Bibliography

OBJECTIVE:To validate the carotid web (CW) risk stratification assessment described in previous works within a larger cohort of patients with symptomatic and incidentally found asymptomatic CWs. METHODS:A retrospective analysis of our institution's electronic medical records identified all patients with a diagnosis of CW from 2017 to 2024. We included symptomatic patients and those with asymptomatic CWs, that is, incidentally found webs without history of stroke or transient ischemic attack. Patient charts were reviewed for demographics, imaging, comorbidities, and a diagnosis of stroke after diagnosis of asymptomatic CW. All angles were measured as described in previous work on a sagittal reconstruction of neck CT angiography in which the common carotid artery (CCA), external carotid artery, and internal carotid artery (ICA) were well visualized, together with the CW itself. Principal component analysis and logistic regression were performed to evaluate the association between high-risk angles and stroke risk.  RESULTS: Twenty-six symptomatic and 26 asymptomatic patients were identified. Of note, the number of patients with hypertension, hyperlipidemia, and smoking history was 17 (65.0%), 16 (62.0%), and 8 (31.0%) for symptomatic patients and 18 (69.0%), 17 (65.0%), and 15 (58.0%) for asymptomatic patients. All angular measurements showed statistically significant associations with stroke status. The CCA-web-pouch angle showed the strongest association (p=2.07×10⁻⁴), followed by the CCA-pouch-tip angle (p=3.23×10⁻⁴), ICA-web-pouch angle (p=0.004), and ICA-pouch-tip angle (p=0.005). Each additional high-risk angle increased the odds of stroke by 9.47-fold (p<0.0001). The associated probability of stroke increased from 6.3% with no high-risk angles to 39.1% with one high-risk angle and further to 85.9% with two high-risk angles. The model demonstrated high sensitivity, correctly identifying 84.6% of positive cases, and high specificity, correctly identifying 88.5% of negative cases. The F1 score was 0.863, indicating good overall model performance.  CONCLUSION: Given this successful stratification of CWs into high- and low-risk groups, the utilization of geometric CW parameters may play a role in improving patient selection for intervention in the setting of incidentally diagnosed CW. .

BACKGROUND AND PURPOSE/OBJECTIVE:Cerebrovascular reactivity (CVR) is a widely studied biomarker of cerebral hemodynamics, commonly used in risk stratification and treatment planning in patients with steno-occlusive disease (SOD). Conventional use relies on normalization of estimates to contralateral hemisphere reference values, which is unsuitable for bilateral or indeterminate distributions of disease. We report upon a custom data-driven approach leveraging random forest classifiers (RFc) to identify candidate voxels for normalization in order to facilitate interrogation outside conditions of known unilateral SOD MATERIALS AND METHODS: We retrospectively analyzed 16 patients with unilateral SOD who underwent acetazolamide-augmented BOLD-MRI and DSC perfusion. Three RFc models were trained using leave-one-out cross-validation (LOOCV) to identify candidate voxels brain-wide whose CVR were within 10% of the normal hemispheric median: i. all voxels; ii. gray matter only; and iii. white matter only. Model input features included time-to-maximum (Tmax), mean transit time (MTT), cerebral blood flow (CBF), and cerebral blood volume (CBV) from contemporaneous DSC. The median model-predicted reference CVR (CVRref) was compared to ground-truth medians in LOOCV, and its impact on threshold-based volumetric classification of CVR reduction assessed. RESULTS:RFc models effectively predicted ground-truth CVR voxels, achieving median absolute percent differences of 12.8% (IQR: 5.0%-18.9%) using all voxels, 11.3% (IQR: 9.3%-16.1%) for gray matter, and 9.8% (IQR: 4.4%-16.9%) for white matter. Volumetric estimates of CVR reduction across thresholds for the models revealed excellent agreement between ground-truth and model estimates without statistically significant differences (p>0.01), excepting lowest white matter CVR thresholds. Model use in a small pilot deployment of bilateral SOD cases demonstrated the potential utility, enabling voxel-wise CVR assessment without reliance on contralateral reference. CONCLUSIONS:We present a novel data-driven approach for normalizing CVR maps in patients with bilateral or indeterminate SOD. Using an RFc, our method provides an individualized, brain-wide reference CVR, expanding the utility of CVR estimates beyond the typical constraints of unilateral disease, and with potential application to other, similarly constrained scenarios such as for SPECT or PET hemodynamic studies. ABBREVIATIONS/BACKGROUND:CVR = cerebrovascular reactivity; RFc = random forest classifier; SOD = steno-occlusive disease.

OBJECTIVE:Common data elements (CDEs) help harmonize data collection across clinical trials and observational studies, allowing for cross-study and cross-condition comparisons. While CDEs exist for multiple clinical conditions and diseases, this work was extended only recently to neurorehabilitation research. DESIGN/METHODS:Subgroups of clinical neurorehabilitation investigators operationalized a domain definition, selected applicable CDEs from 23 existing National Institute of Neurological Disorders and Stroke (NINDS) CDE projects and NIH CDE repositories, and identified areas needing further development. The subgroups also reviewed public comments on the NeuroRehab specific CDEs, which were provided from 01 September 2021 to 07 October 2021. In March 2022, version 1.0 of the NeuroRehab CDEs was completed and can be found on the NINDS CDE website: https://www.commondataelements.ninds.nih.gov/. SETTING/METHODS:NINDS and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)/National Center for Medical Rehabilitation Research (NCMRR) identified NeuroRehab CDEs across 12 different research domains: 1) assessments and examinations; 2) comorbid and behavioral conditions; 3) motor function; 4) treatment/intervention data: therapies; 5) treatment/intervention data: devices; 6) cognitive; 7) communication; 8) emotion/behavior/neuropsychology; 9) activities of daily living/instrumental activities of daily living; 10) quality of life; 11) participation; and 12) infant and pediatrics. Within each domain, corresponding subdomain experts identified instruments with good psychometric measurement properties. PARTICIPANTS/METHODS:120 experts in rehabilitation across the 12 identified research domains and two Co-Chairs with rehabilitation and measurement expertise provided oversight. INTERVENTIONS/METHODS:N/A. MAIN OUTCOME MEASURES/METHODS:CDEs from 23 existing NINDS CDE projects and NIH CDE repositories RESULTS: Clinical investigators recommended NeuroRehab CDEs within three dimensions of the NINDS CDE Classifications: Core, [Disease] Core, and Supplemental - Highly Recommended. Most measures were categorized as Supplemental - Highly Recommended; few were identified as Core or Disease Core. The subgroups also identified measurement gap areas to guide future initiatives as NeuroRehab CDEs are developed in the future. CONCLUSIONS:These efforts are designed to accelerate rehabilitation research in neurological disorders by allowing for cross-study and cross-condition comparisons and to encourage new CDE development.

OBJECTIVE:This study compared outcomes in patients with and without preoperative stress testing undergoing carotid revascularization including carotid endarterectomy (CEA), transfemoral carotid artery stenting (TF-CAS), and transcarotid revascularization (TCAR). METHODS:Patients in the Vascular Quality Initiative Vascular Implant Surveillance and Interventional Outcomes Network (VQI VISION) database who underwent elective carotid revascularization 2016-2020 were included. Patients were analyzed by group based upon whether they underwent cardiac stress testing within two years preceding revascularization without subsequent coronary intervention. Subset analysis was performed comparing outcomes between those with negative and positive results (evidence of ischemia or MI). Outcomes of interest were postoperative MI/neurologic events, 90-day re-admission rates, as well as long-term mortality. RESULTS:We analyzed 18,364 patients (78.8% CEA, 9.3% TF-CAS, 11.9% TCAR). Of these, 35.8% underwent preoperative stress testing (37.4% of CEA patients, 27.5% of TF-CAS patients, and 31.9% of TCAR patients). While comorbidities were significantly higher amongst patients undergoing CEA with preoperative stress test compared to those without stress testing, the overall prevalence of co-morbidities was higher amongst patients undergoing TF-CAS or TCAR irrespective of preoperative stress test status. Compared to patients with a negative stress test, patients with positive stress test undergoing any form of carotid revascularization had a significant increase in 90-day re-admission rates (CEA 19.6% vs 15.8%, p=0.003; CAS 33.3% vs. 18.6%, p<0.001; TCAR 25% vs. 17.5%, p=0.04). No group demonstrated a difference in the incidence of in-hospital postoperative neurologic events or CHF, but those undergoing CEA (but not CAS or TCAR) experienced a significant increase in-hospital post-operative MI (1.7% vs 0.6%, p<0.001). In 3-year follow-up, those with a positive compared to negative stress test were more likely to undergo CABG/PCI in the CEA (adjusted HR 1.87 [1.42-2.27], p<0.0001) and CAS groups (adjusted HR 3.89 [1.77-8.57], p<0.01), but not the TCAR cohort. Notably those undergoing CEA with a positive compared to negative stress test, but not CAS or TCAR, exhibited a 28% increase in mortality (adjusted HR 1.28 [1.03-1.58], p=0.03) at 3 years. Conversely, those patients with a negative stress test compared to no stress test undergoing CEA experienced a 14% reduction in mortality at 3 years (adjusted HR 0.86 [0.76-0.98], p=0.02); this mortality difference was not observed in similar stress test cohort undergoing TF-CAS or TCAR. CONCLUSIONS:Our study highlights that a positive stress test in appropriately selected, asymptomatic patients undergoing elective carotid revascularization can predict select perioperative and long-term cardiovascular outcomes. However, given the high follow-up mortality associated with those undergoing CEA for elective carotid revascularization, our findings call into question whether these patients should be preferentially offered optimal medical management and/or stenting.

After stroke, upper extremity (UE) motor recovery may be mediated in part by transcallosal projections between hemispheres. The interhemispheric competition model posits that transcallosal inhibition (TI) from the contralesional hemisphere is abnormally strengthened following stroke and interferes with motor recovery. This model has recently been questioned. In this longitudinal study, we aimed to definitively confirm or refute a maladaptive role of contralesional TI in subacute motor recovery. We assessed 30 mild-to-moderately impaired subjects over the six months following ischemic stroke. We tracked contralesional TI and motor functions in the proximal and distal segments of the paretic UE. We used transcranial magnetic stimulation to examine the ipsilateral silent period (iSP) in an arm and hand muscle. We used quantitative and clinical testing to examine deficits in muscle strength, motor control, and individuation; UE segmental impairment; and UE activity limitation. We assessed the relationships of contralesional TI to motor functions in the subacute period. Despite recovery of most motor functions in the proximal and distal UE, contralesional TI was largely static and unrelated to recovery of any motor function. There were inconsistent associations between stronger TI, less hand impairment, and less activity limitation in the subacute period overall. We found no compelling evidence to suggest a maladaptive role of contralesional TI in UE motor recovery in mild-to-moderately impaired stroke subjects. The scattered associations between stronger TI and better levels of paretic UE function suggest a potential supportive role rather than a limiting one. These findings challenge the validity of the interhemispheric competition model in the subacute recovery period, and prompt reconsideration of neuromodulatory strategies that subacutely target contralesional TI.

PURPOSE/OBJECTIVE:We describe a case of bilateral, multiple, branch retinal artery occlusions (BRAO) associated with carotid webs. METHODS:A thorough chart review was conducted for the patient. Relevant literature was systematically reviewed. RESULTS:Eight cases of fibromuscular dysplasia (FMD) associated with retinal artery occlusions have been reported. Two additional cases of FMD with other ocular involvement have been described. No cases of carotid webs associated with retinal artery occlusions were found. CONCLUSION/CONCLUSIONS:Carotid webs, an uncommon variant of FMD, are a recognized causative etiology of arterial, ischemic stroke. The case described here of bilateral, multifocal BRAOs represents a unique manifestation of this variant of FMD. This diagnosis should be considered in the setting of an otherwise unrevealing BRAO workup, as recognition of this association may be sight and life-saving.

Typical carotid webs are nonatherosclerotic shelf-like projections of fibromyxoid tissue extending from the posterior wall of the proximal internal carotid artery (ICA). Carotid webs may precipitate acute embolic stroke, especially in younger patients. We describe our experience with pathology-proven carotid webs of atypical appearance, or atypical carotid webs (ACWs), a subset of carotid webs exhibiting abnormal location, morphology, or association with atherosclerotic changes. Our electronic medical record database was queried for all imaging impressions containing "carotid web," "shelf," or "protrusion" from 2018-2024. Imaging was reviewed by an experienced neuroradiologist and neurosurgeon. Patients with typical carotid webs or those with different diagnoses (e.g. dissection/thrombus) were excluded. Twenty-seven patients were treated for typical carotid webs; 24 were treated with carotid endarterectomy (CEA) and had pathology-confirmed webs. Five patients (three male) were identified to have ACWs and included in this report. Mean age was 43.6 years. All ACWs were identified by computed tomography angiography (CTA). All patients presented with acute ischemic stroke or transient ischemic attack (TIA). One web was located on the anterior ICA wall, three were of abnormal morphology different from a "shelf-like" projection, and one was associated with atherosclerotic change. No patients experienced a further stroke or TIA following CEA. ACWs may precipitate ischemic stroke and can be treated and definitively diagnosed with CEA. Due to their unusual appearance, ACWs may evade radiographic identification or be misdiagnosed. As ACWs have not been previously reported in the literature, awareness of their existence must be raised to increase their detection and treatment.

BACKGROUND:Hemorrhagic stroke survivors may have cognitive impairment. We sought to identify preadmission and admission factors associated with cognitive impairment after hemorrhagic stroke. DESIGN/METHODS:Patients with nontraumatic intracerebral or subarachnoid hemorrhage (ICH or SAH) were assessed 3-months post-bleed using the Quality of Life in Neurological Disorders (Neuro-QoL) Cognitive Function short form. Univariate and multivariate analysis were used to evaluate the relationship between poor cognition (Neuro-QoL t-score ≤50) and preadmission and admission factors. RESULTS:Of 101 patients (62 ICH and 39 SAH), 51 (50 %) had poor cognition 3-months post-bleed. On univariate analysis, poor cognition was associated with (p < 0.05): age [66.0 years (52.0-77.0) vs. 54.5 years (40.8-66.3)]; private insurance (37.3 % vs. 74.0 %); BMI > 30 (13.7 % vs. 34.0 %); and admission mRS score > 0 (41.2 % vs. 14.0 %), NIHSS score [8.0 (2.0-17.0) vs. 0.5 (0.0-4.0)], and APACHE II score [16.0 (11.0-19.0) vs. 9.0 (6.0-14.3)]. On multivariate analysis, poor cognition was associated with mRS score > 0 [OR 4.97 (1.30-19.0), p = 0.019], NIHSS score [OR 1.14 (1.02-1.28), p = 0.026], private insurance [OR 0.21 (0.06-0.76), p = 0.017] and BMI > 30 [OR 0.13 (0.03-0.56), p = 0.006]. CONCLUSIONS:Cognitive impairment after hemorrhagic stroke is less common in patients with BMI > 30 and private insurance. Heightened surveillance for non-obese patients without private insurance is suggested. Additional investigation into the relationship between cognition and both BMI and insurance type is needed.

Paired vagus nerve stimulation (VNS) has emerged as a promising strategy to potentiate recovery after neurological injury. This approach, which combines short bursts of electrical stimulation of the vagus nerve with rehabilitation exercises, received approval from the US Food and Drug Aministration in 2021 as the first neuromodulation-based therapy for chronic stroke. Because this treatment is increasingly implemented in clinical practice, there is a need to take stock of what we know about this approach and what we have yet to learn. Here, we provide a survey on the foundational basis of VNS therapy for stroke and offer insight into the mechanisms that underlie potentiated recovery, focusing on the principles of neuromodulatory reinforcement. We discuss the current state of observations regarding synaptic reorganization in motor networks that are enhanced by VNS, and we propose other prospective loci of neuromodulation that should be evaluated in the future. Finally, we highlight the future opportunities and challenges to be faced as this approach is increasingly translated to clinical use. Collectively, a clearer understanding of the mechanistic basis of VNS therapy may reveal ways to maximize its benefits.