Modeling the Mechanical Microenvironment of Coiled Cerebral Aneurysms.

Successful occlusion of cerebral aneurysms using coil embolization is contingent upon stable thrombus formation, and the quality of the thrombus depends upon the biomechanical environment. The goal of this study was to investigate how coil embolization alters the mechanical micro-environment within the aneurysm dome. Inertialess particles were injected in three-dimensional, computational simulations of flow inside patient aneurysms using patient-specific boundary conditions. Coil embolization was simulated as a homogenous porous medium of known permeability and inertial constant. Lagrangian particle tracking was used to calculate the residence time and shear stress history for particles in the flow before and after treatment. The percentage of particles entering the aneurysm dome correlated with the neck surface area before and after treatment (pretreatment: R2 = 0.831, P < 0.001; post-treatment: R2 = 0.638, P < 0.001). There was an inverse relationship between the change in particles entering the dome and coil packing density (R2 = 0.600, P < 0.001). Following treatment, the particles with the longest residence times tended to remain within the dome even longer while accumulating lower shear stress. A significant correlation was observed between the treatment effect on residence time and the ratio of the neck surface area to porosity (R2 = 0.390, P = 0.007). The results of this study suggest that coil embolization triggers clot formation within the aneurysm dome via a low shear stress-mediated pathway. This hypothesis links independently observed findings from several benchtop and clinical studies, furthering our understanding of this treatment strategy.

A Novel Patient-Specific Computational Fluid Dynamics Study of the Activation of Primary Collateral Pathways in the Circle of Willis During Vasospasm.

The Circle of Willis (CoW) is a redundant network of blood vessels that perfuses the brain. The ringlike anatomy mitigates the negative effects of stroke by activating collateral pathways that help maintain physiological perfusion. Previous studies have investigated the activation of these pathways during embolic stroke and internal carotid artery occlusion. However, the role of collateral pathways during cerebral vasospasm-an involuntary constriction of blood vessels after subarachnoid hemorrhage-is not well-documented. This study presents a novel technique to create patient-specific computational fluid dynamics (CFD) simulations of the Circle of Willis before and during vasospasm. Computed tomographic angiography (CTA) scans are segmented to model the vasculature, and transcranial Doppler ultrasound (TCD) measurements of blood flow velocity are applied as boundary conditions. Bayesian analysis leverages information about the uncertainty in the measurements of vessel diameters and velocities to find an optimized parameter set that satisfies mass conservation and that is applied in the final simulation. With this optimized parameter set, the diameters, velocities, and flow rates fall within typical literature values. Virtual angiograms modeled using passive scalar transport agree closely with clinical angiography. A sensitivity analysis quantifies the changes in collateral flow rates with respect to changes in the inlet and outlet flow rates. This analysis can be applied in the future to a cohort of patients to investigate the relationship between the locations and severities of vasospasm, the patient-to-patient anatomical variability in the Circle of Willis, and the activation of collateral pathways.

Direct electrical stimulation of the amygdala enhances declarative memory in humans.

Emotional events are often remembered better than neutral events, a benefit that many studies have hypothesized to depend on the amygdala's interactions with memory systems. These studies have indicated that the amygdala can modulate memory-consolidation processes in other brain regions such as the hippocampus and perirhinal cortex. Indeed, rodent studies have demonstrated that direct activation of the amygdala can enhance memory consolidation even during nonemotional events. However, the premise that the amygdala causally enhances declarative memory has not been directly tested in humans. Here we tested whether brief electrical stimulation to the amygdala could enhance declarative memory for specific images of neutral objects without eliciting a subjective emotional response. Fourteen epilepsy patients undergoing monitoring of seizures via intracranial depth electrodes viewed a series of neutral object images, half of which were immediately followed by brief, low-amplitude electrical stimulation to the amygdala. Amygdala stimulation elicited no subjective emotional response but led to reliably improved memory compared with control images when patients were given a recognition-memory test the next day. Neuronal oscillations in the amygdala, hippocampus, and perirhinal cortex during this next-day memory test indicated that a neural correlate of the memory enhancement was increased theta and gamma oscillatory interactions between these regions, consistent with the idea that the amygdala prioritizes consolidation by engaging other memory regions. These results show that the amygdala can initiate endogenous memory prioritization processes in the absence of emotional input, addressing a fundamental question and opening a path to future therapies.

Medicolegal issues in abusive head trauma for the pediatric neurosurgeon.

The purpose of this article is to serve as a rational guide for the pediatric neurosurgeon in navigating common medicolegal issues that arise in the management of abusive head trauma (AHT). Many of these issues may be unfamiliar or unpleasant to surgeons focused on addressing disease. The authors begin with a brief history on the origins of the diagnosis of AHT and the controversy surrounding it, highlighting some of the facets of the diagnosis that make it particularly unique in pediatric neurosurgery. They then review some special medical considerations in these patients through the perspective of the neurosurgeon and provide several examples as illustration. The authors discuss how to appropriately document these cases in the medical record for expected legal review, and last, they provide an overview of the legal process through which the neurosurgeon may be called to provide testimony.

Awake Mapping of the Auditory Cortex during Tumor Resection in an Aspiring Musical Performer: A Case Report.

INTRODUCTION: Preoperative functional MRI (fMRI) and intraoperative awake cortical mapping are established strategies to identify and preserve critical language structures during neurosurgery. There is growing appreciation for the need to similarly identify and preserve eloquent tissue critical for music production. CASE REPORT: A 19-year-old female musician, with a 3- to 4-year history of events concerning for musicogenic seizures, was found to have a right posterior temporal tumor, concerning for a low-grade glial neoplasm. Preoperative fMRI assessing passive and active musical tasks localized areas of activation directly adjacent to the tumor margin. Cortical stimulation during various musical tasks did not identify eloquent tissue near the surgical site. A gross total tumor resection was achieved without disruption of singing ability. At 9-month follow-up, the patient continued to have preserved musical ability with full resolution of seizures and without evidence of residual lesion or recurrence. CONCLUSION: A novel strategy for performing an awake craniotomy, incorporating preoperative fMRI data for music processing with intraoperative cortical stimulation, interpreted with the assistance of a musician expert and facilitated gross total resection of the patient's tumor without comprising her musical abilities.

Transcranial Doppler ultrasonography in neurological surgery and neurocritical care.

Transcranial Doppler (TCD) ultrasonography is an inexpensive, noninvasive means of measuring blood flow within the arteries of the brain. In this review, the authors outline the technology underlying TCD ultrasonography and describe its uses in patients with neurosurgical diseases. One of the most common uses of TCD ultrasonography is monitoring for vasospasm following subarachnoid hemorrhage. In this setting, elevated blood flow velocities serve as a proxy for vasospasm and can herald the onset of ischemia. TCD ultrasonography is also useful in the evaluation and management of occlusive cerebrovascular disease. Monitoring for microembolic signals enables stratification of stroke risk due to carotid stenosis and can also be used to clarify stroke etiology. TCD ultrasonography can identify patients with exhausted cerebrovascular reserve, and after extracranial-intracranial bypass procedures it can be used to assess adequacy of flow through the graft. Finally, assessment of cerebral autoregulation can be performed using TCD ultrasonography, providing data important to the management of patients with severe traumatic brain injury. As the clinical applications of TCD ultrasonography have expanded over time, so has their importance in the management of neurosurgical patients. Familiarity with this diagnostic tool is crucial for the modern neurological surgeon.

Amygdala-mediated enhancement of memory for specific events depends on the hippocampus.

Emotional events are often remembered better than neutral events, a type of memory prioritization by affective salience that depends on the amygdala. Studies with rats have indicated that direct activation of the basolateral complex of the amygdala (BLA) can enhance memory for neutral events, and if the activation is brief and temporally targeted, can do so in a way that benefits memories for specific events. The essential targets of BLA activation in the case of event-specific memory enhancement were unknown, but the hippocampus was known to receive direct projections from the BLA and to support memory for events. In the present study, rats received counterbalanced infusions of either muscimol, a GABAA receptor agonist, or saline into the hippocampus prior to performing a novel object recognition memory task during which initial encounters with some of the objects were immediately followed by brief electrical stimulation to the BLA. When memory was tested 1day later in the saline condition, rats remembered these objects well but showed no memory for objects for which the initial encounter had not been followed by BLA stimulation. In contrast, no benefit to memory of BLA stimulation was observed in the muscimol condition. The results indicated that brief activation of the BLA can prioritize memories for events by enhancing memory for some object encounters but not others and that this benefit to memory depends on interactions between the amygdala and the hippocampus.

Combination endovascular and microsurgical treatment of partially thrombosed ruptured ICA terminus aneurysm, with common carotid artery to MCA bypass via saphenous vein graft and parent vessel sacrifice after coil embolization.

A 63-year-old woman presented with ruptured giant ICA terminus aneurysm, temporized with coil embolization and definitively treated with parent vessel sacrifice and high-flow bypass.

Craniocervical dural arteriovenous fistula: Microsurgical clipping and technical nuances with ICG.

A 48-year-old male with progressive congestive myelopathy had a craniocvervical DAVF treated with surgical clipping using ICG to confirm solitary inflow.

Brain AVM surgery without endovascular embolization in a low to middle income country.

We treated a 20-year-old woman in Paraguay with a ruptured intraventricular Spetzler-Martin Grade 3 AVM, and illustrate microsurgical resection without embolization in this video.

Nickels and tines: the myth of nickel allergy in intracranial stents.

BACKGROUND: Most intracranial stents contain nickel alloy, and nickel allergy or hypersensitivity is common. Neurological injury following endovascular treatment with a nickel containing intracranial stent has been reported in patients with purported nickel allergy, but it is unclear whether these reactions represent true nickel hypersensitivity. We quantified nickel release from commonly used intracranial stents to investigate whether such stents should be avoided in patients with nickel allergy. METHODS: We examined nickel release from seven commonly used intracranial stents: Enterprise, LVIS Jr, Neuroform, Wingspan, Zilver, Pipeline Flex Embolization Device, and Surpass Evolve. We incubated each stent in human plasma-like media for 30 days. Dimethylglyoxime (DMG) spot testing was performed on each stent to detect released nickel at 0 and 30 days. Inductively coupled plasma-optical emission spectroscopy (ICP-OES) was then used to quantify the nickel concentration of the media at 30 days. Nickel currency and nickel standard for atomic absorption spectrometry were used as positive controls. RESULTS: DMG spot tests indicated nickel release only from nickel currency at 0 and 30 days of incubation. No nickel release was detected from any stent at 30 days using ICP-OES. CONCLUSIONS: Nickel release from commonly used intracranial stents is negligible. These results suggest that previously reported hypersensitivity to these stents may be misattributed to nickel allergy, and that patients with nickel allergy may be safely treated with select nickel-containing stents.

Idiopathic intracranial hypertension imaging approaches and the implications in patient management.

Idiopathic intracranial hypertension (IIH) represents a clinical disease entity without a clear etiology, that if left untreated, can result in severe outcomes, including permanent vision loss. For this reason, early diagnosis and treatment is necessary. Historically, the role of cross-sectional imaging has been to rule out secondary or emergent causes of increased intracranial pressure, including tumor, infection, hydrocephalus, or venous thrombosis. MRI and MRV, however, can serve as valuable imaging tools to not only rule out causes for secondary intracranial hypertension but can also detect indirect signs of IIH resultant from increased intracranial pressure, and demonstrate potentially treatable sinus venous stenosis. Digital subtraction venographic imaging also plays a central role in both diagnosis and treatment, providing enhanced anatomic delineation and temporal flow evaluation, quantitative assessment of the pressure gradient across a venous stenosis, treatment guidance, and immediate opportunity for endovascular therapy. In this review, we discuss the multiple modalities for imaging IIH, their limitations, and their contributions to the management of IIH.

Clinical Utility of Routine Postprocedural Computed Tomography of the Head Following Elective Neuroendovascular Interventions.

BACKGROUND: Little evidence supports acquisition of routine head imaging after uncomplicated elective neurosurgical procedures for patients with unchanged neurological examinations; however, imaging is still performed by some neurointerventionalists. We assessed the clinical utility of routine computed tomography of the head (CTH) following elective neuroendovascular interventions, including aneurysm coiling, aneurysm stent-assisted coiling, aneurysm flow diversion, arteriovenous malformation/fistula embolization, middle meningeal artery embolization for subdural hematoma, extracranial carotid artery stenting, and venous sinus stenting. METHODS: Retrospective chart review identified patients undergoing neuroendovascular intervention from 2011 to 2021 at our institution. Demographic, clinical, and radiographic variables, including presenting signs and symptoms, antiplatelets and/or anticoagulant medications, intraprocedural complications, postprocedural CTH findings, and postprocedural neurological examinations, were recorded. Association of clinical variables with an abnormal postprocedural CTH was assessed with univariate analysis. Patients with ruptured vascular pathology, preoperative embolizations, and missing postprocedural CTH images and/or reports were excluded. RESULTS: Of 509 procedures identified, 354 were eligible for analysis; 4.8% of patients (17/354) had abnormal findings on postprocedural CTH. Nine patients had intraprocedural complications or new postprocedural neurological deficits that would have prompted imaging regardless of institutional practice. None of the remaining 8 (2.3%) patients required additional procedures. New postprocedural neurological deficit was the only significant predictor of abnormal postprocedural CTH (odds ratio = 6.79; 95% confidence interval, 2.01-20.32; P = 0.0009). CONCLUSIONS: In a large cohort of patients undergoing elective neuroendovascular intervention, no patients were identified for whom routine postprocedural CTH alone meaningfully altered their clinical care. Routine CTH is not necessary after uncomplicated elective neuroendovascular interventions performed with careful postprocedural neurological assessment.

Clopidogrel hyper-response increases peripheral hemorrhagic complications without increasing intracranial complications in endovascular aneurysm treatments requiring dual antiplatelet therapy.

Clinical significance of increased clopidogrel response measured by VerifyNow P2Y12 assay is unclear; management guidelines are lacking in the context of neuroendovascular intervention. Our objective was to assess whether increased clopidogrel response predicts complications from endovascular aneurysm treatment requiring dual antiplatelet therapy. A single-institution, 9-year retrospective study of patients undergoing endovascular treatments for ruptured and unruptured aneurysms requiring aspirin and clopidogrel was conducted. Patients were grouped according to preoperative platelet inhibition in response to clopidogrel measured by the VerifyNow P2Y12 assay (VNP; P2Y12 reactivity units, PRU). Demographic and clinical features were compared across groups. Hemorrhagic complication rates (intracranial, major extracranial, minor extracranial) and thromboembolic complications (in-stent stenosis, stroke/transient ischemic attack) were compared, controlling for potential confounders and multiple comparisons. Data were collected from 284 patients across 317 procedures. Pre-operative VNP assays identified 9 % Extreme Responders (PRU ≤ 15), 13 % Hyper-Responders (PRU 16-60), 62 % Therapeutic Responders (PRU 61-214), 16 % Hypo-Responders (PRU ≥ 215). Increased response to clopidogrel was associated with increased risk of any hemorrhagic complication (≤60 PRU vs > 60 PRU; 39 % vs 24 %, P = 0.050); all intracranial hemorrhages occurred in patients with PRU > 60. Thromboembolic complications were similar between therapeutic and subtherapeutic patients (<215 PRU vs ≥ 215 PRU; 15 % vs 16 %, P = 0.835). Increased preoperative clopidogrel response is associated with increased rate of extracranial hemorrhagic complications in endovascular aneurysm treatments. Hyper-responders (16-60 PRU) and Extreme Responders (≤15 PRU) were not associated with intracranial hemorrhagic or thrombotic complications. Hypo-responders who underwent adjustment of antiplatelet therapy and neurointerventions did not experience higher rates of complications.

The impact of the COVID-19 pandemic on cerebrovascular disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a systemic disease that affects nearly all organ systems through infection and subsequent dysregulation of the vascular endothelium. One of the most striking phenomena has been a coronavirus disease 2019 (COVID-19)-associated coagulopathy. Given these findings, questions naturally emerged about the prothrombotic impact of COVID-19 on cerebrovascular disease and whether ischemic stroke is a clinical feature specific to COVID-19 pathophysiology. Early reports from China and several sites in the northeastern United States seemed to confirm these suspicions. Since these initial reports, many cohort studies worldwide observed decreased rates of stroke since the start of the pandemic, raising concerns for a broader impact of the pandemic on stroke treatment. In this review, we provide a comprehensive assessment of how the pandemic has affected stroke presentation, epidemiology, treatment, and outcomes to better understand the impact of COVID-19 on cerebrovascular disease. Much evidence suggests that this decline in stroke admissions stems from the global response to the virus, which has made it more difficult for patients to get to the hospital once symptoms start. However, there does not appear to be a demonstrable impact on quality metrics once patients arrive at the hospital. Despite initial concerns, there is insufficient evidence to ascribe a causal relationship specific to the pathogenicity of SARS-CoV-2 on the cerebral vasculature. Nevertheless, when patients infected with SARS-CoV-2 present with stroke, their presentation is likely to be more severe, and they have a markedly higher rate of in-hospital mortality than patients with either acute ischemic stroke or COVID-19 alone.

Severe, Intolerable Fatigue Associated with Hyperresponse to Clopidogrel.

OBJECTIVE: Clopidogrel is a commonly used antiplatelet agent for the prevention of thromboembolic complications following neuroendovascular procedures, but anecdotal data have raised concern for the possibility that clopidogrel may induce severe, intolerable fatigue. The purpose of this study is to systematically investigate this phenomenon. METHODS: We performed a dual-institution, 9-year, retrospective study of patients undergoing clopidogrel therapy for neuroendovascular procedures. Patients were included only if their response to clopidogrel was assessed by platelet function testing using the VerifyNow P2Y12 (VNP) assay. Hyperresponse to clopidogrel was defined as P2Y12 reaction units ≤60. Patients were considered to have had clopidogrel-induced severe fatigue if the onset of symptoms followed the initiation of clopidogrel therapy; symptoms improved following a reduction in the dose of clopidogrel; and symptoms could not be attributed to any other medical explanation. RESULTS: Data were collected on 349 patients. Five patients (1.4%) met criteria for clopidogrel-induced severe fatigue. All 5 patients were female, ages 39-68. VNP assessments obtained while patients were symptomatic revealed hyperresponse to clopidogrel (0-22 P2Y12 reaction units). Symptoms improved in all 5 patients when the dose of clopidogrel was reduced by half. Notably, 30% of patients (n = 103) demonstrated a hyperresponse to clopidogrel on at least 1 VNP assessment, but 98 of these patients did not suffer from severe fatigue. CONCLUSIONS: A syndrome of severe fatigue and other constitutional symptoms is a rare but clinically significant side effect of hyperresponse to clopidogrel in patients undergoing neuroendovasular intervention.

Endovascular management of iatrogenic dissection into the petrous segment of the internal carotid artery during mechanical thrombectomy for acute stroke.

Iatrogenic dissection of the internal carotid artery is a well-known complication that can occur during mechanical thrombectomy for acute stroke. The vast majority of these injuries are limited to the cervical segment, and only in exceptional circumstances do they require surgical intervention. In the present case, extension of the lesion into the petrous segment of the carotid artery resulted in an acute neurologic decline necessitating emergent endovascular repair. We discuss the nuances of managing an exceptionally rare presentation of this complication.

Case of Esophageal Perforation and Repair with a Supraclavicular Artery Island Fascial Flap 15 Years After Anterior Spine Surgery.

BACKGROUND: Esophageal perforation represents a rare but potentially life-threatening complication of an anterior cervical diskectomy and fusion (ACDF). Delayed presentations of esophageal perforation more than 10 years following surgery are exceedingly rare and difficult to diagnose. Here, we discuss the case of an 80-year-old man who presented to the emergency department with progressive dysphagia 15 years after his ACDF. CASE DESCRIPTION: While prior outpatient workup was suggestive of a diverticulum, there was no evidence of esophageal perforation. Progressive symptoms and repeat imaging on admission were suggestive of retropharyngeal phlegmon. Operative esophagoscopy revealed that the spinal hardware had eroded through the posterior wall of the esophagus, creating a traction diverticulum. The hardware was removed, and the esophageal perforation was closed primarily and buttressed with vascularized tissue from a supraclavicular artery island fascial flap. CONCLUSIONS: This case emphasizes the importance of considering an esophageal perforation in patients who present with dysphagia at any interval following an ACDF, even in the extremely delayed setting. Furthermore, this is the first report, to the best of our knowledge, using a supraclavicular artery island fascial flap to reconstruct an esophageal perforation following an ACDF, and we introduce a novel strategy for managing these complicated injuries.

Human amygdala stimulation effects on emotion physiology and emotional experience.

The amygdala is a key structure mediating emotional processing. Few studies have used direct electrical stimulation of the amygdala in humans to examine stimulation-elicited physiological and emotional responses, and the nature of such effects remains unclear. Determining the effects of electrical stimulation of the amygdala has important theoretical implications for current discrete and dimensional neurobiological theories of emotion, which differ substantially in their predictions about the emotional effects of such stimulation. To examine the effects of amygdala stimulation on physiological and subjective emotional responses we examined epilepsy patients undergoing intracranial EEG monitoring in which depth electrodes were implanted unilaterally or bilaterally in the amygdala. Nine subjects underwent both sham and acute monopolar electrical stimulation at various parameters in electrode contacts located in amygdala and within lateral temporal cortex control locations. Stimulation was applied at either 50 Hz or 130 Hz, while amplitudes were increased stepwise from 1 to 12 V, with subjects blinded to stimulation condition. Electrodermal activity (EDA), heart rate (HR), and respiratory rate (RR) were simultaneously recorded and subjective emotional response was probed after each stimulation period. Amygdala stimulation (but not lateral control or sham stimulation) elicited immediate and substantial dose-dependent increases in EDA and decelerations of HR, generally without affecting RR. Stimulation elicited subjective emotional responses only rarely, and did not elicit clinical seizures in any subject. These physiological results parallel stimulation findings with animals and are consistent with orienting/defensive responses observed with aversive visual stimuli in humans. In summary, these findings suggest that acute amygdala stimulation in humans can be safe and can reliably elicit changes in emotion physiology without significantly affecting subjective emotional experience, providing a useful approach for investigation of amygdala-mediated modulatory effects on cognition.