Ultrasound Blood-Brain Barrier Opening and Aducanumab in Alzheimer's Disease.

Antiamyloid antibodies have been used to reduce cerebral amyloid-beta (Aß) load in patients with Alzheimer's disease. We applied focused ultrasound with each of six monthly aducanumab infusions to temporarily open the blood-brain barrier with the goal of enhancing amyloid removal in selected brain regions in three participants over a period of 6 months. The reduction in the level of Aß was numerically greater in regions treated with focused ultrasound than in the homologous regions in the contralateral hemisphere that were not treated with focused ultrasound, as measured by fluorine-18 florbetaben positron-emission tomography. Cognitive tests and safety evaluations were conducted over a period of 30 to 180 days after treatment. (Funded by the Harry T. Mangurian, Jr. Foundation and the West Virginia University Rockefeller Neuroscience Institute.).

Spinal dural fistula evaluation using 4-Dimensional intra-aortic spinal CTAngiography in a hybrid angiography suite.

Intra-aortic CT Angiography (IA-CTA) is a relatively new technique that shows promise in efficient diagnosis and evaluation of the angioarchitecture of spinal dural arteriovenous fistulae(sdAVF). The authors document the first reported use of a 4D-CT and C-arm fluoroscope in a hybrid interventional suite to evaluate a sdAVF. Time resolved IA-CTA is clinically feasible in the evaluation of sdAVF, has higher temporal resolution as compared to standard IA-CTA and reduced contrast load, radiation dose and potential for procedural complications as compared to standard spinal angiography.

Incidence and Outcomes of Myocardial Infarction in Patients Admitted With Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Data on the incidence and outcomes of acute myocardial infarction (AMI) complicating acute ischemic stroke (AIS) are limited. We aim to evaluate the incidence, treatment patterns, and outcomes of AMI in patients with AIS using a nationwide database. METHODS: The National Inpatient Sample was used to identify patient with AIS between 2003 and 2014. Trends of incidence of AMI and its associated in-hospital mortality were evaluated. Univariate and multivariate logistic regressions were used to evaluate predictors of AMI. The impact of AMI on in-hospital outcomes was assessed in a comparative analysis of propensity-matched groups of patients with and without AMI. RESULTS: Patients with AIS (n=864 043) were identified in the national inpatient sample, of whom 13 573 patients (1.6%) had an AMI (79.5% non-ST-segment-elevation myocardial infarction and 20.5% ST-segment-elevation myocardial infarction). In-hospital mortality was 21.4% and 7.1% in propensity-matched cohorts of patients with and without AMI, P<0.001. In-hospital length of stay and cost of care were 50% higher in the AMI group. In a multivariate logistical regression analysis, the strongest predictors of having AMI after AIS were older age, history of coronary artery disease, chronic renal insufficiency, undergoing mechanical thrombectomy, and rhythm and conduction abnormalities. In the AMI group, undergoing coronary angiography and undergoing percutaneous coronary intervention both strongly correlated with lower in-hospital mortality (odds ratio, 0.34 [confidence interval, 0.23-0.51] and 0.26 [confidence interval, 0.20-0.34], respectively, P<0.001). However, these were only performed in 7.5% and 2% of patients, respectively. CONCLUSIONS: AMI complicating stroke carries a substantial in-hospital mortality and cost of care. Patients who underwent coronary angiography with or without intervention may have improved survival although it was only utilized in a minority of patients. Further studies needed to discern the ideal approach in AMI in patients with AIS.

Circulating extracellular DNA levels are acutely elevated in ischaemic stroke and associated with innate immune system activation.

OBJECTIVE: The objective of this work was to assess the ability of peripheral blood cell-free DNA (cfDNA) levels to identify ischaemic stroke early in the acute phase of care, as well as to examine the relationship between peripheral blood cfDNA levels and stroke-induced innate immune system activation. METHODS: Upon emergency department admission, peripheral blood samples were obtained from 43 patients experiencing acute ischaemic stroke and 20 patients identified as stroke mimics. Plasma cfDNA levels were measured using quantitative polymerase chain reaction (qPCR), infarct volume and NIH stroke scale (NIHSS) were used to assess injury severity, and peripheral blood neutrophil count was used as a measure of innate immune system status. RESULTS: Peripheral blood cfDNA levels were significantly elevated in patients suffering stroke relative to those diagnosed as stroke mimics, and could differentiate between groups with 86% (95% CI = 72-95%) sensitivity and 75% (95% CI = 51-91%) specificity. Furthermore, cfDNA levels displayed significant positive associations between both infarct volume and peripheral blood neutrophil count within the stroke group. CONCLUSIONS: These findings suggest that assessment of peripheral blood cfDNA levels may be useful for the identification of ischaemic stroke in the acute care setting, and provide associative evidence that cfDNA is a potential activator of the peripheral innate immune system in response to cerebral ischaemia.

Transcatheter closure of an aortoatrial fistula following a surgical aortic valve replacement.

Aorto-atrial fistulas are rare complications of aortic valve replacement. We report a case of a post-aortic valve replacement aorto-atrial fistula that was closed percutaneously with an Amplatz Ductal Occluder-II device.

Stereotactic radiosurgery planning based on time-resolved CTA for arteriovenous malformation: a case report and review of the literature.

Stereotactic radiosurgery has long been recognized as the optimal form of management for high-grade arteriovenous malformations not amenable to surgical resection. Radiosurgical plans have generally relied upon the integration of stereotactic magnetic resonance angiography (MRA), standard contrast-enhanced magnetic resonance imaging (MRI), or computed tomography angiography (CTA) with biplane digital subtraction angiography (DSA). Current options are disadvantageous in that catheter-based biplane DSA is an invasive test associated with a small risk of complications and perhaps more importantly, the two-dimensional nature of DSA is an inherent limitation in creating radiosurgical contours. The necessity of multiple scans to create DSA contours for radiosurgical planning puts patients at increased risk. Furthermore, the inability to import two-dimensional plans into some radiosurgery programs, such as Cyberknife TPS, limits treatment options for patients. Defining the nidus itself is sometimes difficult in any of the traditional modalities as all draining veins and feeding arteries are included in the images. This sometimes necessitates targeting a larger volume, than strictly necessary, with stereotactic radiosurgery for treatment of the AVM. In this case report, we show the ability to use a less-invasive and three-dimensional form of angiography based on time-lapsed CTA (4D-CTA) rather than traditional DSA for radiosurgical planning. 4D-CTA may allow generation of a series of images, which can show the flow of contrast through the AVM. A review of these series may allow the surgeon to pick and use a volume set that best outlines the nidus with least interference from feeding arteries or draining veins. In addition, 4D-CTA scans can be uploaded into radiosurgery programs and allow three-dimensional targeting. This is the first reported case demonstrating the use of a 4D CTA and an MRI to delineate the AVM nidus for Gamma Knife radiosurgery, with complete obliteration of the nidus over time and subsequent management of associated radiation necrosis with bevacizumab.

Population-based estimates suggest middle meningeal artery embolization for subdural hematomas could significantly expand the scope of neurovascular therapies.

BACKGROUND: This study quantifies the impact of middle meningeal artery embolization (MMAE) for subdural hematomas (SDHs) by estimating a target population. METHODS: A population-based study at a tertiary hospital, the main SDH facility for a four-county population, used primary ICD-10 codes over 3 years to collate SDH hospitalizations. Clinical and imaging data confirmed traumatic versus non-traumatic and acute versus non-acute (mixed or chronic) SDH. The MMAE-eligible population included patients with non-traumatic, non-acute SDH aged ≥18 years plus patients with 'traumatic' but non-acute SDH aged ≥60 years presenting with a fall. This was contrasted with the rate of large vessel strokes in the same population. RESULTS: 1279 hospitalizations with a primary ICD-10 SDH diagnosis were identified, with 389 from the study population. Excluding repeat admissions, 350 patients were analyzed, 233 (67%) traumatic, and 117 (33%) non-traumatic SDH. Regarding etiology, 'fall ≥60 years' was the most common category in the entire cohort (n=156; 45% (95% CI 39% to 50%)). The SDH rate was 52/100 000 persons/year (95% CI 47 to 57). The rate of all non-traumatic, non-acute SDH in patients aged ≥18 years was 17/100 000 persons/year (95% CI 15 to 20), combining with 'traumatic' but non-acute fall-related SDH in patients aged ≥60 years yielded 41/100 000 persons/year (95% CI 36 to 47). This demographic may represent an MMAE-eligible population, exceeding large vessel stroke rates (31/100 000 persons/year) in the same population, estimating 139 387 potential MMAE cases/year (95% CI 121 517 to 158 168) in the USA. CONCLUSION: MMAE could transform non-acute SDH management, especially in the elderly, potentially surpassing the impact of large vessel stroke. Clinical trials are essential for validation of its efficacy and safety compared with standard management.

MR-guided focused ultrasound thalamotomy for lithium-induced tremor: a case report and literature review.

Drug-induced tremor is a common side effect of lithium with an occurrence of approximately 25% of patients. Cessation of the offending drug can be difficult, and many medical treatments for drug-induced tremor are ineffective. Deep brain stimulation (DBS) has been shown in a limited number of case reports to effectively reduce drug-induced tremor, however, which remains an invasive therapeutic option. MR-guided focused ultrasound (MRgFUS) thalamotomy is an FDA-approved non-invasive treatment for essential tremor (ET). To the best of our knowledge, MRgFUS thalamotomy has never been reported to treat drug-induced tremor. Here, we present a case of a left-handed 55-year-old man with a progressive, medically refractory lithium-induced tremor of the bilateral upper extremities. The patient underwent MRgFUS thalamotomy targeting the right ventral intermediate nucleus (VIM) of the thalamus to treat the left hand. There was almost complete resolution of his left-hand tremor immediately following MRgFUS. There were no side effects. The patient continues to show excellent tremor control at 90-day follow-up and remains free from side effects. This case demonstrates MRgFUS thalamotomy as a possible novel treatment option to treat drug-induced tremor.

Acute ischemic optic neuropathy in a case of heroin overdose.

Presence of acute optic disc and optic nerve infarction in a young man is uncommon finding. This is most commonly seen in the setting of vasculitis and infection. Ischemic optic neuropathy has been reported with cocaine use, amlodipine and alcohol use. To our knowledge there is no reported case of ischemic optic neuropathy in the setting of heroin / opioid use. MR imaging findings in the setting of substance use are similar to other etiologies of ischemic optic neuropathy, with high T2/FLAIR signal, diffusion restriction and abnormal gadolinium enhancement. Here we report a case of 23-year-old man with heroin use disorder presenting with optic nerve infarct resulting in acute painless monocular vision loss.

Synovial fluid biomarkers for periprosthetic infection.

BACKGROUND: We have previously described a unique gene expression signature exhibited by synovial fluid leukocytes in response to bacterial infection, identifying a number of potential biomarkers for infection. However, the diagnostic performance of these potential biomarkers in an immunoassay format is unknown. QUESTIONS/PURPOSES: We therefore evaluated the sensitivity, specificity, and accuracy of several potential synovial fluid biomarkers for infection, and compared them to current standards of testing for periprosthetic infection. METHODS: We prospectively collected synovial fluid from 14 patients classified as having a periprosthetic infection and 37 patients classified as having an aseptic failure. The synovial fluid samples were tested for 23 potential biomarkers for periprosthetic infection. We then determined differences in biomarker levels between infected and aseptic groups, then computed the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for select biomarkers, and finally compared those to current standard tests for infection. RESULTS: Twelve synovial fluid biomarkers had substantially higher average levels in the synovial fluid of infected versus aseptic patients. Synovial fluid levels of IL-1 were a mean of 258 times higher in patients with a periprosthetic infection compared to patients having revision for aseptic diagnoses. Synovial fluid IL-1 and IL-6 levels correctly classified all patients in this study with a sensitivity, specificity, positive predictive value, negative predictive value and accuracy equal to 1. Several markers tested in this study outperformed the ESR and CRP tests. CONCLUSIONS: Patients with a periprosthetic infection have elevated levels of numerous synovial fluid biomarkers, when compared to patients with aseptic diagnoses. Several of these biomarkers exhibited nearly ideal sensitivity, specificity, and accuracy in this study, suggesting that synovial fluid biomarkers could be a valuable tool for diagnosing periprosthetic infection. LEVEL OF EVIDENCE: Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Multiple cerebral cavernous hemangiomas masquerading as hemorrhagic brain metastases.

Intracranial hemorrhagic metastases are a relatively common finding in patients with thyroid carcinoma. Consequently, more unusual vascular lesions may be overlooked in contemplating a differential diagnosis in this patient group. A 50-year-old female with previously treated papillary thyroid carcinoma presented to the emergency department following new onset seizures. Her work up revealed multiple intraparenchymal brain lesions, hyperdense on computed tomography and demonstrating susceptibility effect, T1 shortening and contrast enhancement on magnetic resonance imaging, suggestive of metastases. Subsequent studies revealed lesional architecture consistent with multiple cavernous malformations, made evident by resolution of edema and evolution of blood products. Clinicians should be aware of the possibility of unusual intracranial hemorrhagic lesions in oncology patients which may only become evident on serial imaging evaluation. Cavernous hemangioma has typical MRI characteristic features which includes "mulberry" appearance on T2-weighted and fluid attenuation inversion recovery images with varying internal signal intensity which indicates multiple stages of blood products within the cavernous hamngioma. The lesions commonly have a typical T2-weighted dark hemosiderin rim. Blood sensitive demonstrates prominent surrounding hypointensity representing blooming secondary to internal blood products and/or calcification, if present. Cavernous hemangioma may rarely demonstrate some degree of contrast enhancement. Perfusion imaging may show alteration in capillary permeability involving cavernous malformations which has been previously described in the literature.

Clinical Outcomes of On-Site Versus Off-Site Endovascular Stroke Interventions.

OBJECTIVES: The aim of this study was to assess whether offering local endovascular stroke therapy (EST) rather than transferring patients off-site to receive EST would improve outcomes. BACKGROUND: There are limited data to determine whether offering EST on-site rather than transferring patients to receive EST off-site improves clinical outcomes. METHODS: A large academic consortium database was queried to identify patients with acute ischemic stroke who received EST between October 2015 and September 2019. Primary endpoints were in-hospital mortality and poor functional outcomes. Secondary endpoints were major complications, length of stay, and cost. Baseline characteristics were adjusted for using propensity score matching and multivariate risk adjustment. RESULTS: A total of 22,193 patients with acute ischemic stroke who underwent EST (50.8% on-site, 49.2% off-site) were included. Mean ages were 67.9 ± 15.5 years and 68.4 ± 15.5 years, respectively (p = 0.03). In the propensity score matching analysis, mortality and poor functional outcomes were higher in the off-site EST group (14.7% vs. 11.2% and 40.7% vs. 35.9%, respectively; p < 0.001). In the risk-adjusted analyses with different models, in-hospital mortality and poor functional outcomes remained significantly higher in the off-site EST group. In the most comprehensive model (adjusting for age, sex, demographics, risk factors, tissue plasminogen activator use, and institutional EST volume), in-hospital mortality and poor functional outcomes were significantly higher in the off-site EST group, with odds ratios of 1.38 (95% confidence interval: 1.26 to 1.51) and 1.26 (95% confidence interval: 1.18 to 1.34), respectively (p < 0.001). The incidence of intracranial hemorrhage and mechanical ventilation was higher in the off-site group, but cost was higher in the on-site group in both the propensity score matching and risk-adjusted analyses. CONCLUSIONS: In contemporary U.S. practice, patients with acute ischemic stroke treated with EST on-site had lower in-hospital mortality and better functional outcomes compared with those transferred off-site for EST.

Surgical Thrombectomy for Pulmonary Embolism: Updated Performance Rates and Outcomes.

Treatments for pulmonary embolism are numerous and often complex. Current data on surgical thrombectomy are important but are not readily available. We studied the National Inpatient Sample to evaluate trends in the performance rates and outcomes of surgical thrombectomy in the United States from 2003 through 2014. We think that our findings have meaningful application to the triage and risk stratification of patients who have hemodynamically significant pulmonary embolism.

The 'bendy' basilar: progressive aneurysm tilting and arterial deformation can be a delayed outcome after coiling of large basilar apex aneurysms.

BACKGROUND: Morphological changes in the basilar artery and the artery-aneurysm relationship following coiling of large basilar apex aneurysms may induce morbidity. METHODS: The basilar artery radius-of-curvature was measured along its center line on volumetrically reconstructed images formatted along the plane of curvature. The aneurysm-tilt-angle was measured between the distal basilar and the vertical long axis of the aneurysm. The measurements were compared between small (<10 mm) and large (≥10 mm) aneurysms on baseline and follow-up studies. The volume (mm3) and mass (g) of the deployed coils was also compared. RESULTS: Among 94 consecutive aneurysms, 62 (66%) were <10 mm and 32 (34%) were ≥10 mm. The mean aneurysm size and volume was 9 mm (±4) and 507 mm3(±1366) respectively. The median aneurysm follow-up was 24 months (IQR 6-59). There was no difference between the groups based on age, gender, or associated comorbidities. The coil mass was 0.4 g (±0.2) for aneurysms <10 mm and 1.9 g (±1.6) for aneurysms ≥10 mm (P<0.0001). The total coil volume was 32 (±20) mm3 for aneurysms <10 mm and 187 (±172) mm3 for aneurysms ≥10 mm (P<0.0001). Aneurysms ≥10 mm tilted 13.5o (±14.4) compared with 1.1o (±2.8) for aneurysms <10 mm (P<0.0001). The basilar artery became more curved by 1.3 (±9.4) mm for aneurysms ≥10 mm and 0.25 (±2.1) mm for aneurysms <10 mm (P=0.0002). Other than size of the coiled aneurysms no other factors correlated with the geometrical changes. CONCLUSION: Large coiled basilar apex aneurysms may be more prone to aneurysm tilting and bending of the basilar artery. Speculative causes include the weight of the coil mass and the biomechanical forces exerted on the coiled aneurysm.

Eustachian Tube Foreign Body with Endoscopic-Assisted Surgical Removal.

OBJECTIVES: Foreign bodies of the external and middle ear are not uncommon; however, foreign bodies in the eustachian tube are rare. Here we describe the presentation, imaging, and endoscopic-assisted surgical management of a case of eustachian tube foreign body. METHODS: A 34-year-old male was seen for evaluation of foreign body of the left eustachian tube while working with metal at a machine shop. Imaging and surgical management are highlighted and review of available literature regarding foreign bodies of the eustachian tube is presented. RESULTS: A CT scan revealed a foreign body present approximately 1 cm into the bony eustachian tube. The patient underwent middle ear exploration which required endoscopic assistance to adequately visualize the foreign body. The foreign body was unable to be removed and required the creation of a bony tunnel lateral to the eustachian tube for visualization and access to the foreign body. CONCLUSIONS: This report presents a rare case of eustachian tube foreign body. Use of the endoscope during the surgical removal greatly enhanced the ease and safety of removal. This report also highlights the importance of ear protection with any machining and welding work.

Intravenous thrombolysis before endovascular therapy for large vessel strokes can lead to significantly higher hospital costs without improving outcomes.

BACKGROUND: Limited efficacy of IV recombinant tissue plasminogen activator (rt-PA) for large vessel occlusions (LVO) raises doubts about its utility prior to endovascular therapy. PURPOSE: To compare outcomes and hospital costs for anterior circulation LVOs (middle cerebral artery, internal carotid artery terminus (ICA-T)) treated with either primary endovascular therapy alone (EV-Only) or bridging therapy (IV+EV)). METHODS: A single-center retrospective analysis was performed. Clinical and demographic data were collected prospectively and relevant cost data were obtained for each patient in the study. RESULTS: 90 consecutive patients were divided into EV-Only (n=52) and IV+EV (n=38) groups. There was no difference in demographics, stroke severity, or clot distribution. The mean (SD) time to presentation was 5:19 (4:30) hours in the EV-Only group and 1:46 (0:52) hours in the IV+EV group (p<0.0001). Recanalization: EV-Only 35 (67%) versus IV+EV 31 (81.6%) (p=0.12). Favorable outcome: EV-Only 26 (50%) versus IV+EV 22 (58%) (p=0.45). For patients presenting within 4.5 hours (n=64): Recanalization: EV-Only 21/26 (81%) versus IV+EV 31/38 (81.6%) (p=0.93). Favorable outcome: EV-Only 14/26 (54%) versus IV+EV 22/38 (58%) (p=0.75). There was no significant difference in rates of hemorrhage, mortality, home discharge, or length of stay. A stent retriever was used in 67 cases (74.4%), with similar recanalization, outcomes, and number of passes in the EV-Only and IV+EV groups. The mean (SD) total hospital cost was $33 810 (13 505) for the EV-Only group and $40 743 (17 177) for the IV+EV group (p=0.02). The direct cost was $23 034 (8786) for the EV-Only group and $28 711 (11 406) for the IV+EV group (p=0.007). These significantly higher costs persisted for the subgroup presenting in <4.5 hours and the stent retriever subgroup. IV rt-PA administration independently predicted higher hospital costs. CONCLUSIONS: IV rt-PA did not improve recanalization, thrombectomy efficacy, functional outcomes, or length of stay. Combined therapy was associated with significantly higher total and direct hospital costs than endovascular therapy alone.