Percutaneous transluminal angioplasty and/or stenting for the treatment of basilar artery stenosis: a systematic review and meta-analysis.

PURPOSE: Basilar artery stenosis (BAS) carries high morbidity and mortality, with variable outcomes after endovascular treatments. We systematically reviewed the literature on percutaneous transluminal angioplasty and/or stenting (PTAS) for BAS. METHODS: PubMed, EMBASE, Web-of-Science, Scopus, and Cochrane were searched upon the PRISMA guidelines to include prospective/retrospective cohort studies describing PTAS for BAS. Pooled rates of intervention-related complications and outcomes were analyzed with random-effect model meta-analyses. RESULTS: We included 25 retrospective cohort studies comprising 1016 patients. All patients were symptomatic, presenting with transient ischemic attack or ischemic stroke. BAS frequently involved the middle basilar artery (51.4%), mostly classified as Mori-B (57.4%). PTAS for BAS was indicated in severe (≥ 50-70%), symptomatic BAS refractory to dual antiplatelet therapy. Patients underwent angioplasty (95.5%) and/or stenting (92.2%), preferably using Wingspan or Apollo stents. Median baseline BAS was 81% (range, 53-99%), while median post-intervention BAS was 13% (0-75%). Actuarial rates of successful intervention and "good" final outcome were 100% (95% CI: 100-100%) and 89% (95% CI: 85-93%). Intervention-related recurrent ischemic stroke occurred in 85 patients (8.3%) with actuarial rates of 5% (95% CI: 4-7%), differentiated into perforator (5.4%), in-stent (2.6%), and embolic (0.4%). Actuarial rates of intervention-related dissection, restenosis, and death were 0% (95% CI: 0-0%), 1% (95% CI: 0-1%), and 0% (95% CI: 0-2%). CONCLUSION: Elective PTAS appears to be safe and effective in selected patients with medically refractory, severe, symptomatic, and non-acute BAS. Different stent types and angioplasty-assisted procedures should be considered based on specific clinico-radiological characteristics of the lesions. Future randomized controlled trials are required to corroborate these findings.

Effect of COVID-19 on Emergent Stroke Care: A Regional Experience.

BACKGROUND AND PURPOSE: Anecdotal evidence suggests that the coronavirus disease 2019 (COVID-19) pandemic mitigation efforts may inadvertently discourage patients from seeking treatment for stroke with resultant increased morbidity and mortality. Analysis of regional data, while hospital capacities for acute stroke care remained fully available, offers an opportunity to assess this. We report regional Stroke Team acute activations and reperfusion treatments during COVID-19 mitigation activities. METHODS: Using case log data prospectively collected by a Stroke Team exclusively serving ≈2 million inhabitants and 30 healthcare facilities, we retrospectively reviewed volumes of consultations and reperfusion treatments for acute ischemic stroke. We compared volumes before and after announcements of COVID-19 mitigation measures and the prior calendar year. RESULTS: Compared with the 10 weeks prior, stroke consultations declined by 39% (95% CI, 32%-46%) in the 5 weeks after announcement of statewide school and restaurant closures in Ohio, Kentucky, and Indiana. Results compared with the prior year and time trend analyses were consistent. Reperfusion treatments also appeared to decline by 31% (95% CI, 3%-51%), and specifically thrombolysis by 33% (95% CI, 4%-55%), but this finding had less precision. CONCLUSIONS: Upon the announcement of measures to mitigate COVID-19, regional acute stroke consultations declined significantly. Reperfusion treatment rates, particularly thrombolysis, also appeared to decline qualitatively, and this finding requires further study. Urgent public education is necessary to mitigate a possible crisis of avoiding essential emergency care due to COVID-19.

Understanding the complex pathophysiology of idiopathic intracranial hypertension and the evolving role of venous sinus stenting: a comprehensive review of the literature.

Idiopathic intracranial hypertension (IIH) is a disease defined by elevated intracranial pressure without established etiology. Although there is now consensus on the definition of the disorder, its complex pathophysiology remains elusive. The most common clinical symptoms of IIH include headache and visual complaints. Many current theories regarding the etiology of IIH focus on increased secretion or decreased absorption of cerebrospinal fluid (CSF) and on cerebral venous outflow obstruction due to venous sinus stenosis. In addition, it has been postulated that obesity plays a role, given its prevalence in this population of patients. Several treatments, including optic nerve sheath fenestration, CSF diversion with ventriculoperitoneal or lumboperitoneal shunts, and more recently venous sinus stenting, have been described for medically refractory IIH. Despite the availability of these treatments, no guidelines or standard management algorithms exist for the treatment of this disorder. In this paper, the authors provide a review of the literature on IIH, its clinical presentation, pathophysiology, and evidence supporting treatment strategies, with a specific focus on the role of venous sinus stenting.

Association Between Acute Kidney Disease and Intravenous Dye Administration in Patients With Acute Stroke: A Population-Based Study.

BACKGROUND AND PURPOSE: Computed tomographic angiography and conventional angiography provide timely vascular anatomic information in patients with stroke. However, iodinated contrast dye may cause acute kidney injury (AKI). Within a large, biracial population, we examined in-hospital incidence of new or worsening kidney disease in patients with stroke and its association with administration of intravenous dye. METHODS: All adult residents of the Greater Cincinnati/Northern Kentucky region with acute ischemic stroke or intracerebral hemorrhage who presented to an emergency department in 2010 were included. Prevalence of unsuspected kidney disease at the time of emergency department presentation and the incidence of AKI after admission in 2 groups of patients-those who did and those who did not receive intravenous dye-were determined. RESULTS: In 2010, 2299 patients met inclusion criteria (89% ischemic stroke and 11% intracerebral hemorrhage); mean age 69 years (SD 15), 22% black, and 54% women. Among these patients, 37% had kidney disease at baseline, including 22% (516/2299) in whom this was unsuspected. Two percent (2%; 15/853) of patients with baseline kidney disease developed AKI during the hospital stay. Of those with no baseline kidney disease, 1% (14/14 467) developed AKI. There was no association between dye administration and new or worsening kidney disease. CONCLUSIONS: Although 22% of patients in the Greater Cincinnati/Northern Kentucky stroke population had unsuspected kidney disease, the incidence of new or worsening kidney disease was low, and AKI was not associated with dye administration. These findings confirm single-center reports that the risk of severe renal complications after contrast dye is small.

Advances and challenges in treatment and prevention of ischemic stroke.

We review recent advances in the treatment and prevention of acute ischemic stroke, including the current state of endovascular therapy, in light of 5 randomized controlled trials published this past year. Although no benefit of endovascular therapy over intravenous (IV) recombinant tissue plasminogen activator (rt-PA) has been demonstrated, endovascular therapy is an appropriate treatment for acute ischemic stroke patients within the t-PA window who are ineligible for IV t-PA but have a large vascular occlusion. These trials reveal promises and current limitations of endovascular therapy, and comparison of reperfusion therapies remains an important area of research. One common theme is the strong association between a faster time to reperfusion, improved outcome, and reduced mortality. Primary and secondary stroke prevention trials emphasize the importance of aggressive management of medical risk factors as part of any preventative strategy. New oral anticoagulants, for example, offer cost-effective risk reduction in patients with atrial fibrillation, and may represent an opportunity for those with cryptogenic stroke. We highlight areas of unmet need and promising research in stroke, including the need to deliver proven therapies to more patients, and the need to recruit patients into clinical trials that better define the role of endovascular and other stroke therapies. Finally, improvement in strategies to recover speech, cognition, and motor function has the potential to benefit far more stroke patients than any acute stroke therapy, and represents the greatest opportunity for research in the coming century.

Association between underlying autoimmune disease and small aneurysm size at rupture.

OBJECTIVE: Although the role of inflammation in the development of aneurysms is established, less is known about the development of intracranial aneurysms in the setting of underlying autoimmune disease. The underlying systemic inflammatory characteristics of disorders such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome may influence the development of intracranial aneurysms through common inflammatory pathways. The authors hypothesized that there is an association between underlying autoimmune disease and aneurysm growth and rupture. METHODS: Medical records of patients who underwent cerebral angiography between August 2018 and August 2021 were manually reviewed. Autoimmune diseases as defined for this study are those known to have systemic inflammatory effects on the central nervous system or multiple other organ systems. Statistical analysis, including construction of multivariable linear and logistic regression models, was performed using R version 4.1.0. RESULTS: Chart review identified 190 patients with 469 ruptured and unruptured saccular intracranial aneurysms. There were 31 patients with 44 aneurysms identified as having an autoimmune disease. The mean size of a ruptured aneurysm was significantly smaller among patients with autoimmune disease compared with patients without autoimmune disease (4.14 mm vs 5.34 mm, p = 0.03). The multivariate logistic regression model did not identify any significant association between rupture and autoimmune disease when controlling for other variables (p = 0.49). In the multivariate linear regression model, autoimmune disease was still significantly associated with a smaller size at rupture (p = 0.04), and smoking was associated with a larger size at rupture (p = 0.03) when controlling for other variables. A second multivariate logistic regression model found autoimmune disease to be independently associated with rupture at a size smaller than 7 mm (p = 0.02), while smoking was independently associated with rupture at a size larger than 7 mm (p = 0.01). CONCLUSIONS: Autoimmune disease is associated with a smaller aneurysm size at rupture, although it is not associated with rupture itself. This association may be due to inflammatory pathways that are common to autoimmune diseases as well as aneurysm wall development. Although the authors were unable to identify any association between rupture status and the presence of autoimmune disease, the association between smaller size at rupture and autoimmune disease warrants further studies, as autoimmune disease may influence the trajectory of aneurysm development and the decision to treat.

Complex Morphologic Analysis of Cerebral Aneurysms Through the Novel Use of Fractal Dimension as a Predictor of Rupture Status: A Proof of Concept Study.

BACKGROUND: Aneurysm morphology has been correlated with rupture. Previous reports identified several morphologic indices that predict rupture status, but they measure only specific qualities of the morphology of an aneurysm in a semiquantitative fashion. Fractal analysis is a geometric technique whereby the overall complexity of a shape is quantified through the calculation of a fractal dimension (FD). By progressively altering the scale of measurement of a shape and determining the number of segments required to incorporate the entire shape, a noninteger value for the dimension of the shape is derived. We present a proof-of-concept study to calculate the FD of an aneurysm for a small cohort of patients with aneurysms in 2 specific locations to determine whether FD is associated with aneurysm rupture status. METHODS: Twenty-nine aneurysms of the posterior communicating and middle cerebral arteries were segmented from computed tomography angiograms in 29 patients. FD was calculated using a standard box-counting algorithm extended for use with three-dimensional shapes. Nonsphericity index and undulation index (UI) were used to validate the data against previously reported parameters associated with rupture status. RESULTS: Nineteen ruptured and 10 unruptured aneurysms were analyzed. Through logistic regression analysis, lower FD was found to be significantly associated with rupture status (P = 0.035; odds ratio, 0.64; 95% confidence interval, 0.42-0.97 per FD increment of 0.05). CONCLUSIONS: In this proof-of-concept study, we present a novel approach to quantify the geometric complexity of intracranial aneurysms through FD. These data suggest an association between FD and patient-specific aneurysm rupture status.

Application of the ABCD2 score to identify cerebrovascular causes of dizziness in the emergency department.

BACKGROUND AND PURPOSE: Dizziness can herald a cerebrovascular event. The ABCD(2) score predicts the risk of stroke after transient ischemic attack partly by distinguishing transient ischemic attack from mimics. We evaluated whether this score would also identify cerebrovascular events among emergency department patients with dizziness. METHODS: We retrospectively identified consecutive adults presenting to a university emergency department with a primary symptom of dizziness, vertigo, or imbalance. Two neurologists independently reviewed medical records to determine whether the presenting symptom was caused by a cerebrovascular event (ischemic stroke, transient ischemic attack, or intracranial hemorrhage). ABCD(2) scores were then assigned using clinical information from the medical record. The ability of the score to discriminate between patients with cerebrovascular events and those with other diagnoses was quantified using the c statistic. RESULTS: Among 907 dizzy patients (mean age, 59 years; 58% female), 37 (4.1%) had a cerebrovascular cause, the majority of which were ischemic strokes (n=24). The median ABCD(2) score was 3 (interquartile range, 3-4). The ABCD(2) score predicted ultimate diagnosis of a cerebrovascular event (c statistic, 0.79; 95% CI, 0.73-0.85). Only 5 of 512 (1.0%) patients with a score of ≤ 3 had a cerebrovascular event compared to 25 of 369 patients (6.8%) with a score of 4 or 5 and 7 of 26 patients (27.0%) with a score of 6 or 7. CONCLUSIONS: The ABCD(2) score may provide useful information on dizzy emergency department patients at low-risk for having a cerebrovascular diagnosis and may aid frontline providers in acute management if validated prospectively.

Diminishing returns with successive device passes in mechanical thrombectomy for stroke.

BACKGROUND: Multiple device passes are associated with complications and poor functional outcomes following mechanical thrombectomy (MT) for emergent large vessel occlusion (ELVO). OBJECTIVE: To characterize the relationship between number of device passes, complications, angiographic outcomes, and clinical outcomes in MT for ELVO. METHODS: This is a single-center, retrospective cohort study. Individual device passes for MT were evaluated for any change in Thrombolysis in Cerebral Infarction (TICI) score, successful revascularization (TICI 2b or 3), and complications. Outcomes were compared among groups requiring multiple passes with various cut-off points. Risk factors for unfavorable clinical outcome [90 day modified Rankin Scale > 2] were assessed using multivariate analysis. RESULTS: Successful revascularization was achieved in 75% of 163 patients and 36% required only one device pass. After the second pass, the likelihood of angiographic improvement significantly decreased (p < 0.001). Using multiple cut-off points, higher post-procedural NIHSS scores, mortality rates, and unfavorable 90-day outcomes were associated with a greater number of passes. Multivariate analysis revealed ICA thrombus (comparison: M2, OR: 25, 95% CI 2-275, p = 0.01) and failed revascularization (OR: 68, 95% CI 3.12-1489, p = 0.01) as the only significant predictors of unfavorable clinical outcome. Nonetheless, the likelihood of favorable clinical outcome was higher in patients with an ICA occlusion who were revascularized in < 2 vs. ≥ 2 (44 vs 4%, p = 0.01) or < 3 vs. ≥ 3 (32 vs. 0%, p = 0.02) passes. CONCLUSION: The likelihood of angiographic improvement in patients with ELVO significantly decreases after the second pass. A greater number of passes is associated with worsened clinical outcomes.

Stenting in High-Grade Internal Carotid Artery Stenosis: 2-Dimensional Operative Video.

Carotid artery stenosis is implicated in up to 40% of all ischemic strokes. Accordingly, symptomatic, high-grade carotid artery stenosis portends an especially high risk of future stroke. Intervention via open or endovascular approaches drastically reduces this risk. Under the appropriate conditions, carotid artery stenting serves as a safe and effective alternative to carotid endarterectomy. We present the case of a 57-yr-old male with symptomatic, high-grade stenosis of his right internal carotid artery, for whom a history of radiation to the head and neck represented a relative contraindication to carotid endarterectomy, and thus endovascular treatment with angioplasty and stenting was performed. Informed consent was obtained prior to the procedure. Intraprocedurally, stent delivery past the area of stenosis proved somewhat challenging. However, by employing several nuanced maneuvers, we utilized our guiding catheter in a nonconventional manner in order to successfully perform the procedure. As the field of neuroendovascular surgery evolves, each case provides us unique lessons, which in turn expands our interventional capabilities and adds to the armamentarium of neuroendovascular techniques. We present this surgical video both as a means to provide a general overview of carotid artery stenting, and to share a lesson learned through the implementation of an interesting technical nuance.

An algorithm to improve lateralization accuracy of inferior petrosal sinus sampling: procedural nuances for complex patterns of venous drainage. Patient series.

BACKGROUND: Inferior petrosal sinus sampling (IPSS) is a useful technique in the diagnosis of Cushing's disease (CD) when the imaging finding is negative or equivocal. Different authors have reported considerable variability in the ability to determine tumor laterality with IPSS. Here the authors present a retrospective case series of 7 patients who underwent IPSS using a systematic algorithm to improve lateralization accuracy by identifying optimal sampling sites on the basis of individual cavernous sinus drainage patterns in each patient. OBSERVATIONS: Of the 7 patients identified, 6 were determined to have CD and subsequently underwent surgery. IPSS was accurate in all patients from whom laterality was predicted. Arterial and venous angiography were used to define cavernous sinus drainage patterns and determine optimal sampling sites. All patients who underwent surgery achieved hormonal cure. LESSONS: All IPSS predictions of lateralization were correct when available, and all patients who underwent surgery achieved hormonal cure. Advances in angiographic techniques for identification of the site of primary drainage from the cavernous sinus and subsequent optimization of microcatheter placement may improve the ability to predict tumor laterality.

Massive Orofacial Hemorrhage Treated with the Micro Vascular Plug System.

BACKGROUND: This case series describes the use of the Medtronic Micro Vascular Plug (MVP) system in the treatment of acute massive orofacial hemorrhages in patients with cancer and trauma, resulting in successful hemostasis in these emergent cases. CASE DESCRIPTION: The first case describes a patient who presented with life-threatening oropharyngeal hemorrhage after a motor vehicle accident. In the second case, a patient with oropharyngeal cancer presented with life-threatening bleeding from an ulcerated tumor. Patients were successfully treated with a combination of MVP and coils. Immediate postprocedural imaging confirmed that homeostasis was achieved. CONCLUSIONS: These cases demonstrate that the MVP as an embolic device is a valuable transarterial embolic treatment option in cases of acute orofacial bleeding where rapid, effective hemostasis is required.

Automated CT perfusion imaging for acute ischemic stroke: Pearls and pitfalls for real-world use.

Recent positive trials have thrust acute cerebral perfusion imaging into the routine evaluation of acute ischemic stroke. Updated guidelines state that in patients with anterior circulation large vessel occlusions presenting beyond 6 hours from time last known well, advanced imaging selection including perfusion-based selection is necessary. Centers that receive patients with acute stroke must now have the capability to perform and interpret CT or magnetic resonance perfusion imaging or provide rapid transfer to centers with the capability of selecting patients for a highly impactful endovascular therapy, particularly in delayed time windows. Many stroke centers are quickly incorporating the use of automated perfusion processing software to interpret perfusion raw data. As CT perfusion (CTP) is being assimilated in real-world clinical practice, it is essential to understand the basics of perfusion acquisition, quantification, and interpretation. It is equally important to recognize the common technical and clinical diagnostic challenges of automated CTP including ischemic core and penumbral misclassifications that could result in underestimation or overestimation of the core and penumbra volumes. This review highlights the pitfalls of automated CTP along with practical pearls to address the common challenges. This is particularly tailored to aid the acute stroke clinician who must interpret automated perfusion studies in an emergency setting to make time-dependent treatment decisions for patients with acute ischemic stroke.

Local protein synthesis and spine morphogenesis: Fragile X syndrome and beyond.

Behavioral experiences can modulate neural networks through changes in synaptic morphology and number. In contrast, abnormal morphogenesis of dendritic spines is associated with cognitive impairment, as in Fragile X syndrome. Dendritic or synaptic protein synthesis could provide the specificity and speed necessary for spine morphogenesis. Here, we highlight locally translated proteins shown to affect synaptic morphology (e.g., Fragile X mental retardation protein).

Hippocampal pyramidal cells in adult Fmr1 knockout mice exhibit an immature-appearing profile of dendritic spines.

Fragile X syndrome (FXS) is a common form of mental retardation caused by the absence of functional fragile X mental retardation protein (FMRP). FXS is associated with elevated density and length of dendritic spines, as well as an immature-appearing distribution profile of spine morphologies in the neocortex. Mice that lack FMRP (Fmr1 knockout mice) exhibit a similar phenotype in the neocortex, suggesting that FMRP is important for dendritic spine maturation and pruning. Examination of Golgi-stained pyramidal cells in hippocampal subfield CA1 of adult Fmr1 knockout mice reveals longer spines than controls and a morphology profile that, while essentially opposite of that described in the Fmr1 knockout neocortex, appears similarly immature. This finding strongly suggests that FMRP is required for the processes of spine maturation and pruning in multiple brain regions and that the specific pathology depends on the cellular context.

Aneurysm growth and de novo aneurysms during aneurysm surveillance.

OBJECTIVE Many low-risk unruptured intracranial aneurysms (UIAs) are followed for growth with surveillance imaging. Growth of UIAs likely increases the risk of rupture. The incidence and risk factors of UIA growth or de novo aneurysm formation require further research. The authors retrospectively identify risk factors and annual risk for UIA growth or de novo aneurysm formation in an aneurysm surveillance protocol. METHODS Over an 11.5-year period, the authors recommended surveillance imaging to 192 patients with 234 UIAs. The incidence of UIA growth and de novo aneurysm formation was assessed. With logistic regression, risk factors for UIA growth or de novo aneurysm formation and patient compliance with the surveillance protocol was assessed. RESULTS During 621 patient-years of follow-up, the incidence of aneurysm growth or de novo aneurysm formation was 5.0%/patient-year. At the 6-month examination, 5.2% of patients had aneurysm growth and 4.3% of aneurysms had grown. Four de novo aneurysms formed (0.64%/patient-year). Over 793 aneurysm-years of follow-up, the annual risk of aneurysm growth was 3.7%. Only initial aneurysm size predicted aneurysm growth (UIA < 5 mm = 1.6% vs UIA ≥ 5 mm = 8.7%, p = 0.002). Patients with growing UIAs were more likely to also have de novo aneurysms (p = 0.01). Patient compliance with this protocol was 65%, with younger age predictive of better compliance (p = 0.01). CONCLUSIONS Observation of low-risk UIAs with surveillance imaging can be implemented safely with good adherence. Aneurysm size is the only predictor of future growth. More frequent (semiannual) surveillance imaging for newly diagnosed UIAs and UIAs ≥ 5 mm is warranted.

Pathology of layer V pyramidal neurons in the prefrontal cortex of patients with schizophrenia.

OBJECTIVE: Morphological indications of abnormal circuitry have been detected in the prefrontal neuropil of patients with schizophrenia. The authors tested the hypothesis that schizophrenia is associated with smaller dendritic field size in layer V pyramidal neurons in the prefrontal cortex. METHOD: Tissue from area 10 with a mean postmortem interval of 5.7 hours was obtained from 15 subjects with chronic schizophrenia and 18 normal comparison subjects. After Golgi impregnation, basilar dendritic field size was estimated for layer V pyramidal neurons by ring intersection analysis. RESULTS: The schizophrenia subjects had 40% fewer total ring intersections per neuron than comparison subjects. Smaller basilar dendritic field size was evident in proximal and distal branches. CONCLUSIONS: These results indicate that abnormal dendritic outgrowth or maintenance contributes to reduced neuropil and prefrontal connectivity in schizophrenia. Short postmortem intervals and resulting high tissue quality suggest that these dystrophic changes reflect schizophrenia pathology rather than postmortem artifact.

A brain adaptation view of plasticity: is synaptic plasticity an overly limited concept?

A view that is emerging is that the brain has multiple forms of plasticity that must be governed, at least in part, by independent mechanisms. This view is illustrated by: (1) the apparent separate governance of some non-neural changes by activity, in contrast to synaptic changes driven by learning; (2) the apparent independence of different kinds of synaptic changes that occur in response to the learning aspects of training; (3) the occurrence of separate patterns of synaptic plasticity in the same system in response to different task demands; and (4) apparent dissociations between behaviorally induced synaptogenesis and LTP. The historical focus of research and theory in areas ranging from learning and memory to experiential modulation of brain development has been heavily upon synaptic plasticity since shortly after the discovery of the synapse. Based upon available data, it could be argued that: (1) synaptic, and even neuronal, plasticity is but a small fraction of the range of changes that occur in response to experience; and (2) we are just beginning to understand the importance of these other forms of brain plasticity. Appreciation of this aspect of the brain's adaptive process may allow us to better understand the capacity of the brain to tailor a particular set of changes to the demands of the specific experiences that generated them.

Vertebrobasilar fusiform aneurysms.

Unlike saccular or berry aneurysms, which present more often with subarachnoid hemorrhage, fusiform aneurysms present more often with ischemic stroke or mass effect. The most time-tested treatment of fusiform vertebrobasilar aneurysms consists of flow reduction or flow reversal. Recently, flow diversion has been attempted with mixed results in the posterior circulation. Given the described pathophysiologic processes of fusiform aneurysms that may be altered with modern medical therapies, future investigators may look to medical treatment of these lesions, especially in cases of poor surgical candidates.