Anisetti, Bhrugun

Introduction: Carotid revascularization is known to prevent stroke in patients with high-grade carotid stenosis, but whether carotid revascularization may slow the progression of hemispheric WMD in patients with carotid stenosis to prevent cognitive decline have not been well described. Methods: We conducted a longitudinal study involving patients age ≥40 years with carotid stenosis on ultrasound from 2011-2015 with serial brain MRI scans at least 1 year apart followed for radiographic and clinical outcomes to 2020. Severity of carotid stenosis was defined as moderate 50-69%, high-grade 70-99%, or occluded. Hemispheric WMD volume was quantified from axial T2 FLAIR images. Patients were stratified by revascularization status. Primary outcome was change in WMD volume per year ipsilateral or contralateral to the index carotid. Hemispheric differences in the annual rate of WMD progression (cc/yr) were compared between revascularized vs not revascularized using multivariable linear regression analysis adjusted for variables that differed between revascularization status. Results: Of the 150 patients, moderate stenosis was present in 37.3%, high-grade stenosis in 42.0%, and carotid occlusion in 20.7%. Mean age was 71±10 years, 36.7% were female. Seventy-three (48.7%) had carotid revascularization with a median follow-up of 5.1 years. Baseline WMD volume was 4.86cc ipsilateral and 4.39cc contralateral to the index carotid. Patients who underwent revascularization trended to have slower WMD progression in the hemisphere ipsilateral to the index carotid compared to those not revascularized (0.32cc/yr vs 0.63 cc/yr, p=0.340). The same trend was not observed in the contralateral hemisphere. In adjusted models, carotid revascularization was associated with a 0.33 cc per year decrease in WMD progression between hemispheres compared to those not revascularized (β= -0.33, p=0.070). Conclusions: In this study with a median follow-up of 5 years, we found that carotid revascularization resulted in a 50% reduction in the annual rate of WMD progression. Intervention trials should test whether carotid revascularization slows WMD progression in patients with cognitive impairment to prevent further cerebrovascular events and cognitive decline.

Introduction: Collateral circulation plays a crucial role in determining the extent of brain tissue ischemia and functional outcome in large vessel occlusive (LVO) stroke. Heart failure (HF) is known to cause cerebral hypoperfusion, yet the relationship between HF and robustness of collateral flow has not been well described. Here we hypothesized that HF is associated with poor collateral flow and functional outcome in patients presenting with LVO treated with mechanical thrombectomy (MT). Methods: A single center retrospective study of patients presenting with LVO ischemic stroke who underwent MT between 2012-2020 was done. Single-phase CTA of head prior to MT was used to assess collateral status with poor status defined as ≤ 50% filling and good status as >50% filling. Classification of HF by left ventricular ejection fraction (LVEF) on echocardiogram was used where HF with reduced ejection fraction (HFrEF) had LVEF ≤40%, HF with preserved EF (HFpEF) had LVEF ≥50% with evidence of structural heart disease, and no HF was LVEF≥50% without structural heart disease. Functional outcome was modified Rankin scale (mRS) at 90 days with scores of 0-2 representing good outcome and 3-6 representing poor outcome. Multivariable logistic regression analyses were performed to evaluate the association between HF and poor collaterals after adjusting for vascular risk factors. Results: We identified 235 patients, mean age was 69 ±15 years, median NIHSS was 18, and 45.5% had HF (HFrEF 12.8%, HFmrEF 4.7%, HFpEF 28.1%) while 54.5% had no HF. Poor collaterals were seen in 47.7%, and those with HF were likely to have poor collaterals compared to those without HF (56.1% vs 35.1%, P=.001). There was a dose-dependent relationship between severity of HF and poor collaterals: adjusted odds of poor collaterals were 1.63 and 2.45 in HFpEF and HFrEF, compared to those without HF (trend p=.018). Patients with poor collaterals were likely to have poor outcome at 3 months compared to those with good collaterals (75.0% vs 57.8%; p=.015). Conclusion: Patients with HFrEF were twice as likely to have poor collaterals. This study demonstrated a likely mechanism for poor outcomes seen in ischemic stroke with HF, future studies may explore whether optimization of HF may augment collaterals to improve outcomes.

Introduction: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic, progressive microangiopathy caused by mutations in the NOTCH3 gene. Patients often present with migraine and progressive subcortical infarcts resulting in vascular cognitive impairment and death. Currently, there are no disease modifying treatments. Limiting future trials is the lack of an objective construct to classify and monitor severity of disease. The purpose of this study was to gain experience with a novel CADASIL severity grading system. Methods: Neurologists at 5 academic centers retrospectively reviewed charts of those with confirmed CADASIL. Demographic and clinical data were recorded. The CADASIL severity grades were then assigned: 0 (asymptomatic), 1 (migraine alone), 2 (stroke or mild cognitive impairment), 3 (gait impairment or early dementia) and 4 (bedbound) based on available data. Standard descriptive statistical analyses were used. Results: We identified 138 patients; overall mean age of 50.9±13.1 years, 42.8% were men. 15 (10.9%) were grade 0, 50 (36.2%) were grade 1, 41 (44.2%) were grade 2, 12 (8.7%) were grade 3, and none were grade 4. Those with less severe disease tended to be younger, more likely men, had a lower rate of hypertension and diabetes mellitus and were less frequently tobacco users, Table 1. Increasing number of vascular risk factors was associated with higher severity grading. Conclusion: Our study highlights the ability of this severity scale to separate those with CADASIL into an ordinal system. As known in the literature, more advanced phenotypes of CADASIL tend to have more vascular risk factors. Future trials may consider utilizing this ordinal construct to monitor disease progression, response to therapy, or as a screening tool.

Abstract Purpose Spinal extradural arachnoid cysts (SEDAC) are thought to arise from leakage of CSF through a spinal dural defect. This study investigates the demographics and imaging spectrum of SEDACs at our academic institution and compares them with those reported in the literature. Material and Methods Fifty cases with documented MRI diagnosis of SEDAC, Nabors criteria type I meningeal cyst (MC), were identified from retrospective review of imaging records between 1999 to 2020. Patient demographics, presenting symptoms, cyst characteristics, and management outcomes studied. Statistical analysis to determine associations between maximum cyst size and presenting symptoms along with other imaging findings. Results In all 50 subjects, SEDACs were solitary (single) and sporadic (non-familial). The majority were incidental (62%), located posteriorly (92%) and laterally (80%) in the thoracic and thoracolumbar regions (34%, 30%). They were associated with mild mass effect upon the thecal sac (50%) and bone remodeling (92%). Among symptomatic SEDACs, back pain and radiculopathy were the most reported (68%). Larger cysts were located caudally in the spinal canal, and were associated with greater thecal mass effect, bone remodeling, and septations. Four out of six subjects who underwent surgical management had complete or partial remission. One had cyst recurrence. Conclusion In this largest series of SEDACs, most were discovered incidentally, stable over time, and located in the thoracic spine dorsal to the thecal sac. When symptomatic, back pain and radiculopathy were the most common presenting symptoms. Treatment with complete surgical excision may yield the best results for symptomatic lesions.

Introduction: Patients with carotid stenosis may have silent cerebrovascular disease due to chronic hypoperfusion and atheroembolism. If so, progression of silent disease may be preventable through revascularization. We aim to evaluate the association between carotid stenosis/occlusion and cerebral small vessel disease (SVD) burden ipsilateral to the cervical carotid stenosis. Methods: Patients age ≥40 years with carotid stenosis or occlusion on carotid ultrasound who underwent MRI brain and intracranial angiogram with gradable SVD on MRI from 2011-2015 were included. Severity of carotid stenosis was defined using NASCET criteria as 50-69% (moderate), 70-99% (high-grade), or occluded. WMH volume was quantified using an automated artificial intelligence algorithm applied to axial T2 FLAIR images. Images were also scored for presence of chronic lacune, cerebral microbleeds (CMB), and silent infarcts using STRIVE criteria. Differences in WMD volume between hemispheres ipsilateral and contralateral to the carotid stenosis were calculated, and prevalence of SVD and silent infarct were compared across severities of carotid stenosis. Results: Of the 183 patients, mean age was 71±10 years and 38% were female. Moderate and severe stenosis was present in 36% and 46.5%, respectively, and 18% had carotid occlusion. Mean WMH volume was 7271±522mm 3 . Patients with carotid stenosis had greater WMH volume ipsilateral to the side of carotid stenosis than the contralateral side (mean difference 224±206mm 3 ), and higher severity of stenosis was associated with greater hemispheric difference in WMH volume (moderate vs high; 164±274mm 3 vs 743±309 mm 3 , p=0.009). Silent infarcts were more prevalent in high-grade carotid stenosis than moderate grade (moderate vs high, 10.8% vs 36.5%; p=0.002). There were no differences in either lacunae or CMBs across severities. Conclusions: Greater than one third of patients with high-grade carotid stenosis had ipsilateral silent brain infarction, and the volume of WMH was greater on the side of carotid stenosis. Future analyses should consider the potential yield of screening for carotid atherosclerosis in patients with varying degrees of hemispheric WMH asymmetry.