Strategies to Improve Drug Delivery Across the Blood-Brain Barrier for Glioblastoma.

PURPOSE OF REVIEW: Glioblastoma remains resistant to most conventional treatments. Despite scientific advances in the past three decades, there has been a dearth of effective new treatments. New approaches to drug delivery and clinical trial design are needed. RECENT FINDINGS: We discuss how the blood-brain barrier and tumor microenvironment pose challenges for development of effective therapies for glioblastoma. Next, we discuss treatments in development that aim to overcome these barriers, including novel drug designs such as nanoparticles and antibody-drug conjugates, novel methods of drug delivery, including convection-enhanced and intra-arterial delivery, and novel methods to enhance drug penetration, such as blood-brain barrier disruption by focused ultrasound and laser interstitial thermal therapy. Lastly, we address future opportunities, positing combination therapy as the best strategy for effective treatment, neoadjuvant and window-of-opportunity approaches to simultaneously enhance therapeutic effectiveness with interrogation of on-treatment biologic endpoints, and adaptive platform and basket trials as imperative for future trial design. New approaches to GBM treatment should account for the blood-brain barrier and immunosuppression by improving drug delivery, combining treatments, and integrating novel clinical trial designs.

Evaluation and treatment of headache associated with moyamoya disease - a narrative review.

BACKGROUND: Headache in patients with moyamoya disease is an under-addressed topic in the medical literature. Delay in the diagnosis of moyamoya disease or inappropriate treatment of headache could lead to devastating cerebrovascular outcome. With the evolving understanding of moyamoya disease, migraine pathophysiology, and various migraine-specific medications that have become available, it is crucial to provide an updated overview on this topic. METHODS: We searched PubMed for keywords including moyamoya disease, moyamoya syndrome, headache in moyamoya, surgical revascularization, surgical bypass, migraine and moyamoya, and calcitonin gene-related peptide (CGRP). We summarized the literature and provide a comprehensive review of the headache presentation, possible mechanisms, the impact of various surgical revascularizations on headache in patients with moyamoya disease, and the medical management of headache incorporating novel migraine-specific treatments.Results and conclusion: The most common headache phenotype is migraine; tension-type headache, hemiplegic migraine, and cluster headache have also been reported. Most patients experience improvement of headache after surgical revascularization, though some patients report worsening, or new-onset headache after surgery. Given the complexity of moyamoya disease, careful consideration of different types of medical therapy for headache is necessary to improve the quality of life while not increasing the risk of adverse cerebrovascular events. More prospective studies are warranted to better understand and manage headache in patients with moyamoya disease.

Vessel wall imaging features of Moyamoya disease in a North American population: patterns of negative remodelling, contrast enhancement, wall thickening, and stenosis.

BACKGROUND: This study characterized vessel wall imaging (VWI) features of Moyamoya disease (MMD) in a predominantly adult population at a North American center. METHODS: Consecutive patients with VWI were included. Twelve arterial segments were analyzed for wall thickening, degree and pattern of contrast enhancement, and remodeling. RESULTS: Overall, 286 segments were evaluated in 24 patients (mean age = 36.0 years [range = 1-58]). Of 172 affected segments, 163 (95%) demonstrated negative remodeling. Complete vessel wall obliteration was most frequent in the proximal M1 (17/48, 35%). Affected segments enhanced in 72/172 (42%) (n = 15 for grade II; n = 54 for concentric and n = 18 for eccentric); 20 of 24 (83%) patients had at least one enhancing segment. Both enhancing and non-enhancing segments were present in 19/20 (95%) patients. Vessel wall enhancement was most common in the proximal segments and correlated to the degree of stenosis (p < 0.001), and outer wall diameter (p < 0.001), but not disease duration (p = 0.922) or Suzuki score (p = 0.477). Wall thickening was present in 82/172 (48%) affected segments and was associated with contrast enhancement (p < 0.001), degree of stenosis (p < 0.001), and smaller outer wall diameter (p = 0.004). CONCLUSION: This study presents VWI findings in North American patients with MMD. Negative remodeling was the most common finding. Most patients had both enhancing and non-enhancing abnormal segments. Vessel wall enhancement was most common in proximal segments, variable in pattern or degree and was correlated to the degree of stenosis and smaller outer wall diameter.

Electroencephalogram and heart rate variability features as predictors of responsiveness to vagus nerve stimulation in patients with epilepsy: a systematic review.

INTRODUCTION: Vagus nerve stimulation (VNS) is a mainstay treatment in people with medically refractive epilepsy with a growing interest to identify biomarkers that are predictive of VNS efficacy. In this review, we looked at electroencephalography (EEG) and heart rate variability (HRV) parameters as potential biomarkers. METHODOLOGY: A comprehensive search of several databases limited to the English language and excluding animal studies was conducted. Data was collected from studies that specifically reviewed preoperative EEG and HRV characteristics as predictive factors of VNS outcomes. RESULTS: Ten out of 1078 collected studies were included in this review, of which EEG characteristics were reported in seven studies; HRV parameters were reported in two studies, and one study reported both. For EEG, studies reported a lower global rate of synchronization in alpha, delta, and gamma waves as predictors of the VNS response. The P300 wave, an evoked response on EEG, had conflicting results. Two studies reported high P300 wave amplitudes in nonresponders and low amplitudes in responders, whereas another study reported high P300 wave amplitudes in responders. For HRV, one study reported high-frequency power as the only parameter to be significantly lower in responders. In contrast, two studies from the same authors showed that HRV parameters were not different between responders and nonresponders. CONCLUSION: HRV parameters and EEG characteristics including focal seizures and P300 wave have been reported as potential biomarkers for VNS outcomes in people with medically refractive epilepsy. However, the contradictory findings imply a need for validation through clinical trials.

Intraplaque CTA characteristics as predictors of symptomatology: a semiautomated volumetric analysis.

BACKGROUND: Prior studies comparing CT characteristics of carotid plaques to symptomatology have relied on gross morphologic imaging features. This study sought to determine if volumetric measurements of carotid plaque components are associated with ipsilateral neurologic symptoms. MATERIALS AND METHODS: CTA images of consecutive patients that underwent a carotid endarterectomy were reviewed with a semiautomated software package. Intraplaque volumes of intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), and matrix were computed, as was the degree of arterial stenosis. Statistics were analyzed on a per cerebral hemisphere basis, and dichotomized into symptomatic and asymptomatic. Clinical and radiological endpoints included transient ischemic attack (TIA), ischemic stroke diagnosed on imaging studies, ophthalmologically diagnosed central or branch retinal artery occlusion (RAO), or amaurosis fugax. RESULTS: One hundred sixty-eight carotid plaques were reviewed. The average age is 70.8 years (SD = 8.8); 32/87 (36.8%) were female. Sixty-seven of eighty-seven (77.0%) patients were symptomatic. Sixty-six of one hundred sixty-eight (39.3%) plaques were ipsilateral to the patient's symptoms, while 102/168 (60.7%) were ipsilateral to an asymptomatic hemisphere. Greater intraplaque volumes of IPH (p = 0.03), LRNC (p = 0.008), and matrix (p = 0.0008) were associated with symptoms, as was greater proportion of LRNC in regard to plaque volume (p = 0.04). All but proportion of LRNC remained statistically significant after adjustment for plaque size. More severe luminal stenosis was also associated with ipsilateral neurologic symptoms, both when calculated by smallest diameter or by area (p < 0.0001 for both). CONCLUSION: Higher volumes of intraplaque IPH, LRNC, matrix, and degree of arterial stenosis are associated with ipsilateral neurologic symptoms. Greater intraplaque proportions of LRNC are also associated with ipsilateral ischemic manifestations, suggesting that larger relative composition of lipids may be particularly predictive of symptomatology.

Histological composition of retrieved emboli in acute ischemic stroke is independent of pre-thrombectomy alteplase use.

BACKGROUND AND PURPOSE: Given recent evidence suggesting the clot composition may be associated with revascularization outcomes and stroke etiology, clot composition research has been a topic of growing interest. It is currently unclear what effect, if any, pre-thrombectomy thrombolysis has on clot composition. Understanding this association is important as it is a potential confounding variable in clot composition research. We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients who did and did not receive pre-treatment tPA to study the effect of tPA on clot composition. MATERIALS AND METHODS: Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using Martius Scarlett Blue (MSB) staining and area of the clot was also measured on the gross photos. Student's t test was used for continuous variables and chi-squared test for categorical variables. RESULTS: A total of 1430 patients were included in this study. Mean age was 68.4±13.5 years. Overall rate of TICI 2c/3 was 67%. A total of 517 patients received tPA (36%) and 913 patients did not (64%). Mean RBC density for the tPA group was 42.97±22.62% compared to 42.80±23.18% for the non-tPA group (P=0.89). Mean WBC density for the tPA group was 3.74±2.60% compared to 3.42±2.21% for the non-tPA group (P=0.012). Mean fibrin density for the tPA group was 26.52±15.81% compared to 26.53±15.34% for the non-tPA group (P=0.98). Mean platelet density for the tPA group was 26.22±18.60% compared to 26.55±19.47% for the non-tPA group (P=0.75). tPA group also had significantly smaller clot area compared to non-tPA group. CONCLUSIONS: Our study 1430 retrieved emboli and ischemic stroke patients shows no interaction between tPA administration and clot composition. These findings suggest that tPA does not result in any histological changes in clot composition.

Semiautomated carotid artery plaque composition: are intraplaque CT imaging features associated with cardiovascular risk factors?

BACKGROUND: Little remains known about the connection between cardiovascular (CV) risk factors and carotid plaque morphologies. This study set out to assess for any such associations. MATERIALS AND METHODS: A retrospective review was completed of consecutive patients that had CTA neck imaging prior to CEA. Body mass index (BMI), tobacco and/or alcohol use, and history of diabetes and/or hypertension were collected from patients' medical records. Lab values were dichotomized based on values: total cholesterol < 200 or ≥ 200; low-density lipoprotein (LDL) < 130 or ≥ 130, high-density lipoprotein < 35 or ≥ 35, and triglycerides < 200 or ≥ 200. A semiautomated analysis of CTA images computed maximum stenosis, intraplaque volumes of intraplaque hemorrhage, lipid-rich necrotic core (LRNC), and matrix, and intraplaque volume and proportional plaque makeup of calcifications of each carotid plaque. RESULTS: Of 87 included patients, 54 (62.1%) were male. Mean age was 70.1 years old. Both diabetes and hypertension were associated with greater intraplaque calcification volume (p = 0.0009 and p = 0.01, respectively), and greater proportion of calcification within a plaque (p = 0.004 and p = 0.01, respectively). Higher BMI was associated with greater intraplaque volume of LRNC (p=0.02) and matrix (0.0007). Elevated total cholesterol was associated with both larger intraplaque calcification volume (p = 0.04) and greater proportion of calcification within a plaque (p = 0.01); elevated LDL was associated with greater intraplaque calcification volume (p = 0.005). CONCLUSION: Multiple CV risk factors are associated with morphological differences in carotid artery plaques. Dysregulation of both total cholesterol and LDL and higher BMI are associated with higher volumes of intraplaque LRNC, a marker of plaque vulnerability.

Cardiac manifestations in a western moyamoya disease population: a single-center descriptive study and review.

An embryological association between moyamoya disease (MMD) and cardiac manifestations has been proposed. Data up to this point remains anecdotal, and the prevalence of cardiac manifestations in a western MMD population is uncertain. The objective of this study was to determine the prevalence of cardiac manifestations including coronary artery disease (CAD) and congenital cardiac defects in a mostly Caucasian population of MMD patients and review prior reports of such cases. Medical records of MMD patients who presented to our institution between 1990 and 2019 were retrospectively reviewed for the presence of various congenital cardiac malformations and concomitant CAD. The prevalence of congenital cardiac defects and CAD was determined. A literature search for prior cases of MMD with concomitant cardiac manifestations was performed. A total of 181 MMD patients were included in our analysis, 139 (76.8%) of whom were Caucasian. Ten patients had cardiac manifestations (5.5%). There were six total MMD patients with congenital cardiac defects (3.3%). All patients with congenital defects were diagnosed in childhood. The prevalence of congenital defects in MMD was slightly higher than the general population as reported previously (0.8-1.2%). Four MMD patients had CAD (2.2%). The mean age of patients with CAD was 41.0 years (SD = 12.3, range = 33-59) in our series and 33.1 years (SD = 15.0) in a review of prior reports. These mean ages of CAD are in contrast to the 7th and 8th decades of lifein the general population as indicated by prior studies. Our findings support an association between MMD and cardiac manifestations. Further investigation is warranted in order to further characterize this potential relationship and shed light on a possible cardio-cephalic neural crest syndrome.

Carotid Intraplaque Hemorrhage Is Associated with Cardiovascular Risk Factors.

INTRODUCTION: Intraplaque hemorrhage (IPH) is a known predictor of symptomatic cervical carotid artery disease. However, the association between IPH and modifiable cardiovascular risk factors, patient demographics, and pertinent laboratory values has not been extensively studied. METHODS: A retrospective review was performed of consecutive patients who have undergone dedicated carotid plaque imaging over a 3-year period. Patients were excluded if the MR examination did not include high-resolution carotid plaque imaging. Intraplaque hyperintense signal on carotid plaque images was presumed to represent IPH. The presence or absence of IPH was compared to various demographic and clinical variables. Multivariable regression analysis was performed in order to determine an independent association between variables and IPH. RESULTS: Of 643 included patients, 114 patients (17.7%) had IPH in one or both carotids, 529 patients (82.3%) did not; 39.5% of patients with IPH had coronary artery disease compared to 23.1% of patients without (p = 0.0003). Patients with IPH also had higher proportions of hypertension (77.2 vs. 60.7%, p = 0.009), hyperlipidemia (HLD; 89.5 vs. 62.4%, p < 0.0001), diabetes mellitus (29.0 vs. 18.7%, p = 0.01), and a history of tobacco smoking (63.2 vs. 52.6%, p = 0.003). Patients without IPH had, on average, higher high-density lipoprotein levels (46.1 vs. 56.7%, p = 0.003). Factors independently associated with IPH were advanced age (odds ratio [OR]: 1.1, 95% CI: [1.0-1.05], p <0.0001), male sex (OR: 2.5, 95% CI: [1.4-4.4], p = 0.0001), presence of carotid stenosis (OR: 8.4, 95% CI: [4.6-15.3], p < 0.0001), and HLD (OR: 2.6, 95% CI: [1.3-5.2], p = 0.009). CONCLUSIONS: IPH is associated with multiple cardiovascular risk factors, in particular advanced age, male sex, presence of carotid stenosis, and HLD. Such risk factors likely play a role in the development of IPH and may provide insight into the pathophysiology of unstable carotid plaques.

Standardized Fabrication Method of Human-Derived Emboli with Histologic and Mechanical Quantification for Stroke Research.

BACKGROUND: As access to patient emboli is limited, embolus analogs (EAs) have become critical to the research of large vessel occlusion (LVO) stroke and the development of thrombectomy technology. To date, techniques for fabricating standardized human blood-derived EAs are limited in the variety of compositions, and the mechanical properties relevant to thrombectomy are not quantified. METHODS: EAs were made by mixing human banked red blood cells (RBCs), plasma, and platelet concentrate in 10 different volumetric percentage combinations to mimic the broad range of patient emboli causing LVO strokes. The samples underwent histologic analysis and tensile testing to mimic the pulling action of thrombectomy devices, and were compared to patient emboli. RESULTS: EAs had histologic compositions of 0-96% RBCs, 0.78%-92% fibrin, and 2.1%-22% platelets, which can be correlated with the ingredients using a regression model. At fracture, EAs elongated from 81% to 136%, and the ultimate tensile stress ranged from 16 to 949 kPa. These EAs' histologic compositions and tensile properties showed great similarity to those of emboli retrieved from LVO stroke patients, indicating the validity of such EA fabrication methods. EAs with lower RBC and higher fibrin contents are more extensible and can withstand higher tensile stress. CONCLUSIONS: EAs fabricated and tested using the proposed new methods provide a platform for stroke research and pre-clinical development of thrombectomy devices.

Expression and cellular localization of the transcription factor NeuroD1 in the developing and adult rat pineal gland.

Circadian rhythms govern many aspects of mammalian physiology. The daily pattern of melatonin synthesis and secretion is one of the classic examples of circadian oscillations. It is mediated by a class of neuroendocrine cells known as pinealocytes which are not yet fully defined. An established method to evaluate functional and cytological characters is through the expression of lineage-specific transcriptional regulators. NeuroD1 is a basic helix-loop-helix transcription factor involved in the specification and maintenance of both endocrine and neuronal phenotypes. We have previously described developmental and adult regulation of NeuroD1 mRNA in the rodent pineal gland. However, the transcript levels were not influenced by the elimination of sympathetic input, suggesting that any rhythmicity of NeuroD1 might be found downstream of transcription. Here, we describe NeuroD1 protein expression and cellular localization in the rat pineal gland during development and the daily cycle. In embryonic and perinatal stages, protein expression follows the mRNA pattern and is predominantly nuclear. Thereafter, NeuroD1 is mostly found in pinealocyte nuclei in the early part of the night and in cytoplasm during the day, a rhythm maintained into adulthood. Additionally, nocturnal nuclear NeuroD1 levels are reduced after sympathetic disruption, an effect mimicked by the in vivo administration of α- and ß-adrenoceptor blockers. NeuroD1 phosphorylation at two sites, Ser(274) and Ser(336) , associates with nuclear localization in pinealocytes. These data suggest that NeuroD1 influences pineal phenotype both during development and adulthood, in an autonomic and phosphorylation-dependent manner.

Interhemispheric Contralateral Transcallosal Approach to a Giant Thalamic Cavernous Malformation: 2-Dimensional Operative Video.

Thalamic cavernous malformations are challenging lesions to approach given their deep location and proximity to eloquent neurovascular structures. Several approaches to this region exist, and small nuances in the location of the lesion dictate different surgical trajectories. For cavernous malformations presenting to the superomedial surface of the thalamus, the interhemispheric transcallosal approach affords an excellent trajectory as the anterior two-thirds of the superomedial thalamus constitutes the lateral aspect of the floor of the body of the lateral ventricle. In addition, when the cavernous malformation extends laterally, the contralateral adjunct of the interhemispheric transcallosal approach provides optimal visualization of the lateral aspect of the lesion. In this video, we present the case of a 31-year-old woman who presented to our institution with a giant hemorrhagic thalamic cavernous malformation that resulted in rapid neurological decline characterized by ataxia, right hemiparesis, and diplopia. The cavernous malformation was removed using an interhemispheric contralateral transcallosal approach. The patient had near complete resolution of her preoperative deficits with mild residual weakness in her right hand at 3-month follow-up. At 3-year follow-up, magnetic resonance imaging revealed no active cavernous malformation, and the patient had no recurrence of symptoms. This manuscript was conducted in accordance with the ethical standards of our institution's Institutional Review Board. The patient gave informed consent for surgery and video recording.

Middle meningeal artery embolization for chronic subdural hematoma: A single-center experience and predictive modeling of outcomes.

BACKGROUND: Remarkable interest is rising around middle meningeal artery embolization (MMAE) as an emerging alternative therapy for chronic subdural hematoma (cSDH). The study aims to highlight a large center experience and the variables associated with treatment failure and build experimental machine learning (ML) models for outcome prediction. MATERIAL AND METHODS: A 2-year experience in MMAE for managing patients with chronic subdural hematoma was analyzed. Descriptive statistical analysis was conducted using imaging and clinical features of the patients and cSDH, which were subsequently used to build predictive models for the procedure outcome. The modeling evaluation metrics were the area under the ROC curve and F1-score. RESULTS: A total of 100 cSDH of 76 patients who underwent MMAE were included with an average follow-up of 6 months. The intervention had a per procedure success rate of 92%. Thrombocytopenia had a highly significant association with treatment failure. Two patients suffered a complication related to the procedure. The best performing machine learning models in predicting MMAE failure achieved an ROC-AUC of 70%, and an F1-score of 67%, including all patients with or without surgical intervention prior to embolization, and an ROC-AUC of 82% and an F1-score of 69% when only patients who underwent upfront MMAE were included. CONCLUSION: MMAE is a safe and minimally invasive procedure with great potential in transforming the management of cSDH and reducing the risk of surgical complications in selected patients. An ML approach with larger sample size might help better predict outcomes and highlight important predictors following MMAE in patients with cSDH.

Arteriovenous shunts of the cervical spine: patient demographics, presentation, patterns of high-risk venous drainage, and updated classification.

BACKGROUND: Intracranial dural arteriovenous (AV) fistula classifications focus on presence/absence of retrograde flow in the cortical veins of the brain as this angiographic finding portends a worse prognosis. However, prior categorization systems of AV shunts in the spine do not incorporate these features. We propose an updated classification for spinal shunting lesions that terms any shunting lesion with retrograde flow in any cortical vein of the brain or spinal cord medullary vein as "high risk". To present this classification, we analyzed our center's most recent experience with cervical spine shunting lesions. METHODS: The electronic medical record at our institution was reviewed to identify shunting lesions of the cervical spine and patient demographics/presentation. Comprehensive craniospinal digital subtraction angiograms were evaluated to classify shunt location, type (arteriovenous malformation (AVM) vs arteriovenous fistula (AVF)), and presence of high-risk venous drainage. RESULTS: Some 52 lesions were identified and categorized as pial/dural/epidural/paravertebral AVFs and intramedullary/extraspinal AVMs. Lesions were classified as high risk or not depending on the presence of retrograde flow into at least one vein that directly drains the spinal cord or brain. All patients who presented with either hemorrhage or infarct had underlying high-risk lesions. Additionally, 50% (17/34) of symptomatic patients with high-risk lesions presented with neurological extremity symptoms (OR=10.0, p=0.037) most of which fit a myelopathic pattern. CONCLUSION: We present an updated classification system for shunting lesions of the spine that focuses on high-risk retrograde flow to the brain or spine in addition to anatomical location in order to better inform patient management.

Revascularization of a Complex Case of Vertebrobasilar Insufficiency with Occipital Artery-Anterior Inferior Cerebellar Artery Bypass.

Atherosclerotic disease is the most common etiology in causing posterior circulation strokes and can be found within the intracranial vertebrobasilar system.1 Endovascular and surgical approaches to treat this disease have been defined with both advantages and disadvantages.2,3 We present a case of surgical revascularization of a complex case of vertebrobasilar insufficiency with occipital artery (OA)-anterior inferior cerebellar artery (AICA) bypass (Video 1). A 56-year-old gentleman presented with severe, disabling, and progressive symptoms of vertebrobasilar insufficiency refractory to maximal medical management. Symptom onset was 2 years prior after suffering a left lateral medullary stroke due to a left vertebral artery (VA) occlusion. Angiography showed left VA occlusion after the origin of the posterior inferior cerebellar artery (PICA) and a hypoplastic right VA mostly ending in a PICA with a small and critically stenosed branch to the basilar artery. An initial attempt to revascularize the chronic totally occluded left VA using a combination of anterograde and retrograde (via PComm) approaches was unsuccessful. The decision was made to proceed with an OA-AICA bypass. The end-to-side anastomosis was conducted in the right cerebellopontine cistern and was uncomplicated. Postoperative angiography demonstrated a patent bypass with brisk OA-to-AICA flow with retrograde filling of the basilar artery and its branches. No perioperative strokes. The patient remained free of recurrent symptoms of vertebrobasilar insufficiency at 6 months' follow-up.

Use of intravascular optical coherence tomography to confirm the diagnosis of a carotid web in a patient with recurrent ipsilateral embolic strokes and evaluate the response to stenting.

A Carotid web (CaW) is defined as a focal shelf-like projection of non-atheromatous, fibrous tissue along the posterior wall of the carotid bulb. CaW are rare and commonly overlooked lesions increasingly recognized as a cause of stroke in otherwise healthy patients. Intravascular imaging modalities such as intravascular ultrasound and optical coherence tomography (OCT) have been proposed as an adjunct to digital subtraction angiography for the evaluation of CaW. However, the use of OCT in CaW has yet to be described. This report investigated the utility of OCT as an adjunct imaging modality in the evaluation of CaW morphology in a young patient with recurrent ischemic strokes.

Endovascular revascularization of chronically occluded common carotid artery for symptomatic cerebral hypoperfusion.

Endovascular recanalization is increasingly being utilized in symptomatic patients with chronically occluded carotid arteries.1 In carefully selected patients, endovascular recanalization has shown to lower the risk of ischemic events when compared to medical management alone.1 However, successful endovascular revascularization is technically challenging and not without risk.1, 2 In this video, we demonstrate a case of a 64-year-old woman who presented with recurrent transient ischemic attacks. On imaging she was found to have a chronic total occlusion of the common carotid artery from the arch. After obtaining informed consent, the patient underwent a successful endovascular recanalization and stenting of a chronically occluded left common carotid artery with aid from an intravascular guided re-entry catheter. Post operatively the patient developed a neck hematoma which improved and she returned to her neurological baseline. She reported no further symptoms on her three month follow up.