Search

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.

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.

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.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.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).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.

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.

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

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.

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.

BackgroundMost 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.MethodsWe 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.ResultsDMG 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.ConclusionsNickel 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.

IntroductionTransradial access is increasingly used among neurointerventionalists as an alternative to the transfemoral route. Currently available data, building on the interventional cardiology experience, primarily focus on right radial access. However, there are clinical scenarios when left-sided access may be indicated. The purpose of this study was to evaluate the technical feasibility of left transradial access to cerebral angiography across three institutions.MethodsA retrospective chart review was performed for patients who underwent cerebral angiography accessed via the left radial artery at three institutions between January 2018 and July 2019. The outcome variables studied were successful catheterization, vascular complications, and fluoroscopic time.ResultsNineteen patients underwent a total of 25 cerebral angiograms via left transradial access for cerebral aneurysms (n=15), basilar occlusion (n=1), carotid stenosis (n=1), arteriovenous malformation (n=1), and cervical neurofibroma (n=1). There were 12 diagnostic angiograms and 13 interventional angiograms. The left transradial approach was chosen due to left vertebrobasilar pathology (n=22), right subclavian stenosis (n=2), and previous right arm amputation (n=1). There was one instance of radial artery spasm, which resolved after catheter removal, and one conversion to transfemoral access in an interventional case due to lack of distal catheter support. There were no procedural complications.ConclusionsLeft transradial access in diagnostic and interventional cerebral angiography is a technically feasible, safe, and an effective alternative when indicated, and may be preferable for situations in which pathology locations or anatomic limitations preclude right-sided radial access.

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.

Objective: Chronic subdural hematomas (cSDH) are an increasingly prevalent neurological disease that often requires surgical intervention to alleviate compression of the brain. Management of cSDHs relies heavily upon computed tomography (CT) imaging, and serial imaging is frequently obtained to help direct management. The volume of hematoma provides critical information in guiding therapy and evaluating new methods of management. We set out to develop an automated program to compute the volume of hematoma on CT scans for both preoperative and postoperative images. Methods: A total of 128 CT scans (21,710 images) were manually segmented and used to train a convolutional neural network to automatically segment chronic subdural hematomas. We included both preoperative and postoperative coronal head CTs from patients undergoing surgical management of cSDHs. Results: Our best model achieved a Dice score of 0.8351 on the testing dataset and an average Dice score of 0.806 +/- 0.06 on the validation set. This model was trained on the full data set with reduced volumes, a network depth of 4, and post activation residual blocks within the context modules of the encoder pathway. Patch trained models did not perform as well and decreasing the network depth from 5 to 4 did not appear to significantly improve performance. Conclusions: We successfully trained a convolutional neural network on a dataset of pre and postoperative head CTs containing cSDH. This tool could assist with automated, accurate measurements for evaluating treatment efficacy.

Objective Chronic subdural hematomas (cSDHs) are an increasingly prevalent neurologic disease that often requires surgical intervention to alleviate compression of the brain. Management of cSDHs relies heavily on computed tomography (CT) imaging, and serial imaging is frequently obtained to help direct management. The volume of hematoma provides critical information in guiding therapy and evaluating new methods of management. We set out to develop an automated program to compute the volume of hematoma on CT scans for both pre- and postoperative images. Methods A total of 21,710 images (128 CT scans) were manually segmented and used to train a convolutional neural network to automatically segment cSDHs. We included both pre- and postoperative coronal head CTs from patients undergoing surgical management of cSDHs. Results Our best model achieved a DICE score of 0.8351 on the testing dataset, and an average DICE score of 0.806 ± 0.06 on the validation set. This model was trained on the full dataset with reduced volumes, a network depth of 4, and postactivation residual blocks within the context modules of the encoder pathway. Patch trained models did not perform as well and decreasing the network depth from 5 to 4 did not appear to significantly improve performance. Conclusions We successfully trained a convolutional neural network on a dataset of pre- and postoperative head CTs containing cSDH. This tool could assist with automated, accurate measurements for evaluating treatment efficacy.

Introduction Despite advancements in endovascular treatment of intracranial aneurysms, up to 30% recur and require additional treatment. Predicting outcomes after aneurysm treatment with flow-diverting stents (FDS) could impact treatment strategy and avoid unnecessary follow-up. Computational fluid dynamics (CFD) techniques have been used to simulate the effect of treatment on the intracranial aneurysm hemodynamics, and to quantify change in certain hemodynamics factors that can be associated with treatment success or failure. We use CFD simulations, based on aneurysm anatomy and patient-specific blood flow and pressure data, to study which hemodynamics factors are predictive of six-month treatment outcomes. Materials and Methods Twenty-four patients with n=25 unruptured intracranial aneurysms treated with FDS were included (Table 1). 3-dimensional rotational angiographic anatomy was used to create the computational model and intraoperative blood velocity and blood pressure measurements proximal to the aneurysm, obtained with an endovascular dual-sensor microwire, were used as boundary conditions for CFD simulations before and after FDS treatment. For post-treatment calculations, a virtual stent based on the Pipeline Flex Embolization Device was deployed into the CFD simulations. Hemodynamics factors within the aneurysm dome including flow into aneurysm (Q), wall shear stress (WSS), wall shear stress gradient (WSSG), viscous dissipation, oscillatory shear index (OSI), and relative residence time (RRT) were calculated before and after FDS placement. Aneurysm treatment was classified as success or failure based on six-month follow-up angiography. Hemodynamics changes between immediate post-treatment and pre-treatment simulations were associated to treatment outcomes. Results Marked reduction in Q, WSS, WSSG, and OSI were seen in most cases immediately after FDS treatment compared to the pretreatment values, indicative of the redirection of blood flow along the neck plane. Reduction of Q at peak systole and increase in RRT in the aneurysm dome were strong predictors of FDS treatment success. Further multivariate analysis of hemodynamic predictors of treatment outcome will be presented. Conclusion Patient-specific CFD simulations using intraoperative physiological velocity and pressure data have been performed pre- and immediately post-treatment. Hemodynamics factors have the potential to predict aneurysm treatment outcomes, making them valuable for neurointerventionalists to consider in treatment planning. Disclosures D. Lim: None. L. March: None. M. Barbour: None. H. Haughn: None. S. Levy: None. K. Prijoles: None. D. Bass: None. G. Barros: None. C. Kelly: None. F. Chassagne: None. A. Aliseda: None. M. Levitt: 1; C; Philips Volcano. L. Kim: None.

Introduction Embolic coils are a preferred endovascular treatment technique for intracranial aneurysms, but approximately 34% of these treatments are unsuccessful, requiring re-treatment. To better understand why endovascular treatment fails, we used computational fluid dynamics (CFD) simulations to determine the changes in hemodynamics factors after coil embolization that were associated with treatment success versus those that led to failure. We incorporated patient-specific intravascular blood flow measurements as boundary conditions, which has been shown to improve simulation accuracy. Materials and Methods Adult patients presenting with unruptured intracranial aneurysms treated with coil embolization were enrolled. 3D-rotational angiograms taken before and immediately after treatment were used to create computational models of the patients’ vasculature. Intraoperative blood velocity and blood pressure measurements were obtained before and immediately after coil embolization by placing a dual-sensor microwire (ComboWire) in the proximal segment of the parent vessel. These measurements were incorporated as patient-specific boundary conditions for the CFD simulations to compute hemodynamics conditions before and after treatment. Hemodynamics variables including inflow rate (Q), wall shear stress (WSS), and wall shear stress gradient (WSSG) were calculated within each aneurysm. Treatment success or failure was determined by evaluating each patient’s most recent follow-up angiogram, and this outcome was then correlated to the changes in hemodynamics variables pre- and post-treatment. This statistical analysis aims to determine associations between immediate changes in post-treatment hemodynamics variables and treatment outcomes. Results Sixteen patients were included (table 1). Regardless of long-term treatment outcome, immediate post-treatment reductions were observed in Q, WSS and WSSG. Preliminary analyses suggest that an increase in shear stress at the aneurysm neck was associated with successful long-term outcome, representative of the significant redirection of blood flow velocity by the coil mass required to prevent aneurysm recanalization. Final multivariate analyses will be presented. Conclusion CFD simulations of aneurysm hemodynamics using patient-specific imaging and boundary conditions were performed in a large cohort of patients treated with coil embolization. Increases in neck plane shear and redirection of blood flow found immediately post-coil embolization have the potential to predict long-term treatment success. Disclosures S. Levy: None. L. Marsh: None. M. Barbour: None. K. Prijoles: None. D. Lim: None. H. Haughn: None. C. Kelly: None. F. Chassange: None. G. Barros: None. D. Bass: None. A. Aliseda: None. M. Levitt: 1; C; Philips Volcano. L. Kim: None.

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.

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.

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.

Objective Patients with medically intractable epilepsy often undergo sequential surgeries and are therefore exposed to an elevated risk for infection, resulting in unanticipated returns to the operating room. The goal of our study was to determine whether use of an osteoplastic bone flap technique would reduce the infection rate in these patients. Methods A single-institution, retrospective chart review of patients with medically intractable epilepsy for grid placement was performed. Univariate analyses and linear regression were used to assess primary outcomes, including infection and hematomas requiring surgical evacuation. Secondary outcomes included duration of treatment and other, unanticipated surgeries. Results A total of 199 patients were identified, 56 (28%) with osteoplastic flaps. Standard free flaps were associated with an increased rate of infection at the craniotomy site (n = 24, 17%, vs. 0, 0%, P = 0.003), whereas osteoplastic flaps were associated with more returns to operating room for hematoma evacuation (n = 5, 9% vs. 3.2%, P = 0.024). Overall, the rate of return to operating room for unanticipated surgeries was similar, but infectious complications prolonged the duration of treatment (median: 17 days vs. 2 days, χ2 = 13.97, P Conclusions Osteoplastic bone flaps markedly decreased the risk of craniotomy infections compared with free flaps in patients undergoing sequential surgeries. This decrease is offset, however, by an increase in intracranial hematoma requiring return to the operating room. Infection appeared to be a more significant complication as it was associated with increased duration of treatment. The osteoplastic technique is especially appealing in those patients likely to undergo multiple surgeries in short succession.

Cerebral arteriovenous malformations (AVMs) are complicated lesions representing a wide spectrum of pathology. They are frequently associated arterial aneurysms and venous varices, the latter of which carry a particularly high risk of rupture. AVM rupture commonly results in hydrocephalus, but there are a rare number of cases in which hydrocephalus develops as a result of an unruptured AVM. An elderly woman with a benign medical history presented to an outside hospital with 5 days of progressively worsening headaches that she described as retroorbital, dull, and lateralizing to the right. Workup at an outside hospital with a brain magnetic resonance image (MRI) and a head computed tomography angiogram (CTA) revealed concern for a tectal AVM with an associated venous varix abutting the tectal plate. Four weeks later, her headaches and diplopia had significantly improved. A diagnostic cerebral angiogram revealed that venous varix had decreased in size and a subsequent CTA showed interval improvement of her hydrocephalus. By the following month, her clinical signs and symptoms had completely resolved. Resolution of the patient’s symptoms clearly correlated with multiple radiographic findings, and therefore it seems reasonable to assume that expansion of the varix was the inciting event that lead to the development of her symptoms. Although this case reflects an exceptional series of events, it helps emphasize the point that a shunt or a ventriculostomy may not be necessary in a patient presenting with hydrocephalus from an unruptured AVM.

The present review highlights results from recent studies that delivered brief electrical stimulation to the basolateral complex of the amygdala in rats to reveal its capacity to prioritize declarative memories on a moment-to-moment basis even after the moment has passed. The results indicate that this memory enhancement depends on the hippocampus and elicits intrahippocampal gamma synchrony that possibly corresponds with sharpened hippocampal spike-timing dependent plasticity. These recent findings are discussed in relation to past studies of emotional memory in rodents and humans.

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.

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.

Activation of the amygdala either during emotional arousal or by direct stimulation is thought to enhance memory in part by modulating plasticity in the hippocampus. However, precisely how the amygdala influences hippocampal activity to improve memory remains unclear. In the present study, brief electrical stimulation delivered to the basolateral complex of the amygdala (BLA) following encounters with some novel objects led to better memory for those objects one day later. Stimulation also elicited field-field and spike-field CA3-CA1 synchrony in the hippocampus in the low gamma frequency range (30-55 Hz), a range previously associated with spike timing and good memory. Additionally, the hippocampal spiking patterns observed during BLA stimulation reflected recent patterns of activity in the hippocampus. Thus, the results indicate that amygdala activation can prioritize memory consolidation of specific object encounters by coordinating the precise timing of CA1 membrane depolarization with incoming CA3 spikes to initiate long-lasting spike-timing dependent plasticity at putative synapses between recently active neurons.

Arteriovenous malformations (AVMs) are typically considered congenital lesions, although there is growing evidence for de novo formation of these lesions as well. The authors present the case of an AVM in the same cerebral cortex that had been affected by a severe traumatic brain injury (TBI) more than 6 years earlier. To the best of the authors' knowledge, this is the first report attributing the formation of an AVM directly to TBI.

Dear Editor: We read with great interest the recent report by Yeo and colleagues [2] describing two cases of de novo AVMs in children. Their cases and literature review provide further evidence that AVMs, especially in children, are dynamic lesions that can appear and change throughout a patient’s lifetime. Our recent publication [1], which was not included in their review, provides another case example of de novo formation of a pediatric AVM. Like the majority of patients described in their review, our patient had a history of a possible inciting event (a severe traumatic brain injury) that may have contributed to formation of the AVM. Additionally, the patient we described presented with seizures, as did one of the patients described by Yeo and colleagues. This reinforces the fact that new neurologic symptoms must be investigated with appropriate studies even in patients who have previously undergone neuroimaging.

Objective Many surgical interventions have emerged as effective means of restoring mechanical stability of the anterior column of the spine. The lateral extracavitary approach (LECA) allows for broad visualization and circumferential reconstruction of the spinal column. However, early reports demonstrated significant complication rates, protracted operative times, and prolonged hospitalizations. More recent reports have highlighted concerns for subsidence, particularly with expandable cages. Our work seeks to describe a single-surgeon consecutive series of patients undergoing LECA for thoracic corpectomy. Specifically, the objective was to explore the surgical considerations, clinical and radiographic outcomes, and complication profile of this approach. Methods A retrospective study examined data from 17 consecutive patients in whom single or multi-level corpectomy was performed via a LECA by a single surgeon. Vertebral body replacement was achieved with either a static or expandable titanium cage. The Karnofsky Performance Scale (KPS) was utilized to assess patient functional status before and after surgery. Radiographic outcomes, particularly footplate-to-body ratio and subsidence, were assessed on CT imaging at 6 weeks after surgery and at follow-up of at least 6 months. Results The majority of patients had post-operative KPS scores consistent with functional independence (≥70, 12/17 patients, 71%). Fourteen patients had improved or maintained function by last follow-up. In both groups, all patients had a favorable footplate-to-body ratio, and rates of subsidence were similar at both time points. Notably, the overall complication rate (24%) was significantly lower than that published in the literature, and no patient suffered a pneumothorax that required placement of a thoracostomy tube. Conclusion The LECA approach for anterior column reconstruction with static or expandable cages is an important surgical consideration with favorable surgical parameters and complication rates. Further, use of expandable cages may allow for reconstruction over a larger segment without increased risk of subsidence.

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.

The basolateral complex of the amygdala (BLA) modulates memory for emotional events, and direct activation of the BLA following a learning session can enhance subsequent memory. Yet optimal enhancement of episodic memory during emotional events would likely require that BLA activation occur close in time to the event and to be brief enough to target specific memories if some events are to be remembered better than others. In the present study, rats were given a novel object recognition memory task in which initial encounters with some of the objects were immediately followed by brief electrical stimulation of the BLA, and these objects were remembered better one day later as compared to objects for which the initial encounter was not followed by stimulation. The results indicated that BLA stimulation can enhance memory for individual events, a necessary ability for the BLA to modulate episodic memory effectively.

Mutations in the Leucine Rich Repeat Kinase 2 (LRRK2) gene, first described in 2004 have now emerged as the most important genetic finding in both autosomal dominant and sporadic Parkinson’s Disease (PD). While a formidable research effort has ensued since the initial gene discovery, little is known of either the normal or the pathological role of LRRK2. We have created lines of mice that express human mutant wild-type (hWT) or G2019S Lrrk2 via bacterial artificial chromosome (BAC) transgenesis. In vivo analysis of the dopaminergic system revealed abnormal dopamine neurotransmission in both hWT and G2019S transgenic mice evidenced by a decrease in extra-cellular dopamine levels, which was detected without pharmacological manipulation. Immunopathological analysis revealed changes in localization and increased phosphorylation of microtubule binding protein tau in G2019S mice. Quantitative biochemical analysis confirmed the presence of differential phospho-tau species in G2019S mice but surprisingly, upon dephosphorylation the tau isoform banding pattern in G2019S mice remained altered. This suggests that other post-translational modifications of tau occur in G2019S mice. We hypothesize that Lrrk2 may impact on tau processing which subsequently leads to increased phosphorylation. Our models will be useful for further understanding of the mechanistic actions of LRRK2 and future therapeutic screening.