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Objective: Mind-wandering is a pervasive human brain state and, when in excess, may promote negative affect and neuropsychiatric conditions. Mindfulness meditation may promote alternate brain states, improving affect and reducing stress. An understanding of the neural basis between these brain states could thus advance treatment of neuropsychiatric conditions, including those associated with epilepsy., Methods: To explore the neural basis of mindfulness meditation versus mind-wandering, we enrolled eight patients in a trial of structured mindfulness meditation and open mind-wandering who underwent stereo electroencephalography (sEEG) within the mesial temporal lobe for seizure localization. Electrophysiology was compared between mind-wandering and mindfulness separately for epileptic and non-epileptic MTL. Using fitting-one-over-f modeling, periodic components of electrophysiology were compared in canonical frequency bands of theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz), and gamma (30-55 Hz). Aperiodic components of the power spectra were assessed by the model offset, knee, and exponent., Results: We found a significant reduction in gamma power (30-55 Hz) within the mesial temporal lobe (MTL) during mindfulness meditation compared with mind-wandering in non-epileptic (p = 1.20E-4) but not in epileptic MTL (p = 0.352).There was also a significant difference between epileptic versus non-epileptic MTL in gamma power between conditions (p = 0.011). There were no significant changes in power across any frequency band within epileptic mesial temporal MTL between brain states. Conversely, there were significant differences between mind-wandering and mindfulness within epileptic MTL in aperiodic components (offset, knee, and exponent, all p < 0.05), while no differences in aperiodic components were seen in non-epileptic MTL (all p > 0.70)., Significance: Intracranial electrophysiologic modulations between brain state (mind-wandering versus mindfulness) may differ between epileptic and non-epileptic MTL. Modulations in gamma activity in non-epileptic MTL may represent functional changes in brain state, while aperiodic changes in epileptic MTL may modulate propensity for seizures., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Fedor Panov, MD is a paid speaker for NeuroPace. The remaining authors have no conflicts of interest. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Herpes simplex virus encephalitis (HSVE) is associated with significant morbidity and mortality. Here, we present the occurrence of HSVE in a 36-year-old immunocompetent patient following craniotomy for a traumatic acute subdural hematoma (ASDH)., Methods: Imaging after four days of progressive headache following a fall with head-strike demonstrated a 1 cm thick left holohemispheric ASDH with significant cerebral compression, edema, and 8 mm of left-to-right midline shift, and an emergent craniotomy and ASDH evacuation were performed, with additional treatment needed for reaccumulation. Postoperatively, the patient developed a worsening leukocytosis, became febrile, and was hypotensive requiring vasopressor support., Results: Despite empiric antibiotics, the patient remained persistently febrile with significant leukocytosis. Repeat head CT showed a new left insular hypodensity and a subsequent viral encephalitis panel was positive for HSV-1. The patient was then started on intravenous acyclovir, with progressive neurological exam improvement. Of note, the patient was noted to have a positive serum HSV-1 IgG antibody titer, indicative of prior infection., Conclusions: Given the known systemic immunosuppression in brain injury and the high prevalence of HSV seropositivity, clinicians should consider the possibility of HSVE from HSV reactivation in TBI patients with persistent fever, leukocytosis, and/or neurological deficits without an obvious etiology.

Quantification of motor symptom progression in Parkinson's disease (PD) patients is crucial for assessing disease progression and for optimizing therapeutic interventions, such as dopaminergic medications and deep brain stimulation. Cumulative and heuristic clinical experience has identified various clinical signs associated with PD severity, but these are neither objectively quantifiable nor robustly validated. Video-based objective symptom quantification enabled by machine learning (ML) introduces a potential solution. However, video-based diagnostic tools often have implementation challenges due to expensive and inaccessible technology, and typical "black-box" ML implementations are not tailored to be clinically interpretable. Here, we address these needs by releasing a comprehensive kinematic dataset and developing an interpretable video-based framework that predicts high versus low PD motor symptom severity according to MDS-UPDRS Part III metrics. This data driven approach validated and robustly quantified canonical movement features and identified new clinical insights, not previously appreciated as related to clinical severity, including pinkie finger movements and lower limb and axial features of gait. Our framework is enabled by retrospective, single-view, seconds-long videos recorded on consumer-grade devices such as smartphones, tablets, and digital cameras, thereby eliminating the requirement for specialized equipment. Following interpretable ML principles, our framework enforces robustness and interpretability by integrating (1) automatic, data-driven kinematic metric evaluation guided by pre-defined digital features of movement, (2) combination of bi-domain (body and hand) kinematic features, and (3) sparsity-inducing and stability-driven ML analysis with simple-to-interpret models. These elements ensure that the proposed framework quantifies clinically meaningful motor features useful for both ML predictions and clinical analysis., (© 2024. The Author(s).)

Objective: Neurosurgical targeting of the cerebellar dentate nucleus via ablative dentatotomy and stimulation of the dentate nucleus was historically used for effective treatment of spasticity. Yet for decades, neurosurgical treatment of spasticity targeting the cerebellum was bypassed in favor of alternative treatments such as intrathecal baclofen pumps and selective dorsal rhizotomies. Cerebellar neuromodulation has recently reemerged as a promising and effective therapy for spasticity and related movement disorders., Methods: In this narrative review, the authors contextualize the historical literature of cerebellar neuromodulation, comparing it with modern approaches and exploring future directions with regard to cerebellar neuromodulation for spasticity., Results: Neurosurgical intervention on the cerebellum dates to the use of dentatotomy in the 1960s, which had progressed to electrical stimulation of the cerebellar cortex and dentate nucleus by the 1980s. By 2024, modern neurosurgical approaches such as tractography-based targeting of the dentate nucleus and transcranial magnetic stimulation of cerebellar cortex have demonstrated promise for treating spasticity., Conclusions: Cerebellar neuromodulation of the dentate nucleus and cerebellar cortex are promising therapies for severe cases of spasticity. Open areas for exploration in the field include the following: tractography-based targeting, adaptive cerebellar stimulation, and investigations into the network dynamics between the cerebellar cortex, deep cerebellar nuclei, and the subcortical and cortical structures of the cerebrum.

Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus (GP) is an established therapy for Parkinson's disease (PD). Novel DBS devices can record local field potential (LFP) physiomarkers from the STN or GP. While beta (13-30 Hz) and gamma (40-90 Hz) STN and GP LFP oscillations correlate with PD motor severity and with therapeutic effects of treatments, STN-GP interactions in electrophysiology in patients with PD are not well characterized., Methods: Simultaneous bilateral STN and GP LFPs were recorded in a patient with PD who received bilateral STN-DBS and GP-DBS. Power spectra in each target and STN-GP coherence were assessed in various ON- and OFF-levodopa and DBS states, both at rest and with voluntary movement., Results: OFF-levodopa and OFF-DBS, beta peaks were present at bilateral STN and GP, coincident with prominent STN-GP beta coherence. Levodopa and dual-target-DBS (simultaneous STN-DBS and GP-DBS) completely suppressed STN-GP coherence. Finely-tuned gamma (FTG) activity at half the stimulation frequency (62.5 Hz) was seen in the STN during GP-DBS at rest. To assess the effects of movement on FTG activity, we recorded LFPs during instructed movement. We observed FTG activity in bilateral GP and bilateral STN during contralateral body movements while on GP-DBS and ON-levodopa. No FTG was seen with STN-DBS or dual-target-DBS., Conclusion: Dual-target-DBS and levodopa suppressed STN-GP coherence. FTG throughout the basal ganglia was induced by GP-DBS in the presence of levodopa and movement. This bilateral STN-FTG and GP-FTG corresponded with the least severe bradykinesia state, suggesting a pro-kinetic role for FTG., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pulsatile tinnitus (PT) may be due to a spectrum of cerebrovascular etiologies, ranging from benign venous turbulence to life threatening dural arteriovenous fistulas. A focused clinical history and physical examination provide clues to the ultimate diagnosis; however, the predictive accuracy of these features in determining PT etiology remains uncertain., Methods: Patients with clinical PT evaluation and DSA were included. The final etiology of PT after DSA was categorized as shunting, venous, arterial, or non-vascular. Clinical variables were compared between etiologies using multivariate logistic regression, and performance at predicting PT etiology was determined by area under the receiver operating curve (AUROC)., Results: 164 patients were included. On multivariate analysis, patient reported high pitch PT (relative risk (RR) 33.81; 95% CI 3.81 to 882.80) compared with exclusively low pitch PT and presence of a bruit on physical examination (9.95; 2.04 to 62.08; P=0.007) were associated with shunting PT. Hearing loss was associated with a lower risk of shunting PT (0.16; 0.03 to 0.79; P=0.029). Alleviation of PT with ipsilateral lateral neck pressure was associated with a higher risk of venous PT (5.24; 1.62 to 21.01; P=0.010). An AUROC of 0.882 was achieved for predicting the presence or absence of a shunt and 0.751 for venous PT., Conclusion: In patients with PT, clinical history and physical examination can achieve high performance at detecting a shunting lesion. Potentially treatable venous etiologies may also be suggested by relief with neck compression., Competing Interests: Competing interests: MRA: board member: Mind Rhythm; consultancy: Stryker, Neurovascular, Covidien, and MicroVention; comments: pipeline proctor for Covidien and PHIL DSMB for MicroVention; patents (planned, pending, or issued): cerebral venous sinus stent; comments: provisional patent serial No 62/984,549. KHN: consultancy: Stryker Neurovascular and Imperative Care., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Randomized controlled trial (RCT) evidence has revealed the efficacy of vagus nerve stimulation (VNS) paired with rehabilitation therapy, over therapy alone, for upper-limb functional recovery after ischemic stroke. However, this technique has not yet been described for the recovery of chronic motor deficits after hemorrhagic stroke., Observations: Three years after left putaminal intracerebral hemorrhagic stroke with chronic upper-limb functional deficits, a patient was treated with VNS for enhanced stroke recovery. VNS was paired with 6 weeks of in-clinic physical therapy, resulting in upper-limb functional improvement of 14 points on the Fugl-Meyer Assessment Upper Extremity (FMA-UE) index for stroke recovery (maximum score of 66 equating to normal function). This improvement was more than 1 standard deviation above the improvement documented in the first successful RCT of VNS paired with therapy for ischemic stroke (5.0 ± 4.4 improvement on FMA-UE)., Lessons: VNS is a promising therapy for enhanced recovery after hemorrhagic stroke and may offer greater improvement in function compared to that after ischemic stroke. Improvement in function can occur years after the time of intracerebral hemorrhage.

Background: The aim of this study was to examine associations between genomic alterations in brain metastases and common preoperative imaging findings including overt intratumoral hemorrhage, cystic features, and edema., Methods: A single-center, retrospective study was performed including patients who underwent surgical resection of brain metastasis with available preoperative magnetic resonance imaging (MRI). Next-generation sequencing of more than 500 coding genes was performed on the resected brain metastases. Preoperative MRI was reviewed to identify the presence of intratumoral hemorrhage, cystic features, and edema in the resected brain metastasis. Genomic data were then correlated with the imaging features using univariate and multivariate nominal logistic regression analyses., Results: We included 144 brain metastases from 141 patients in the study cohort. Half (72) of the metastases had an intratumoral hemorrhage, 26 (18%) had cystic features, and 130 (90%) had edema. Mutations in TP53 were associated with a reduced risk of intratumoral hemorrhage (odds ratio [OR] 0.2, 95% confidence interval [CI] 0.07-0.5, P < 0.001). Mutations in RB1 and CCND1 were associated with elevated risk of the metastasis having cystic features (OR 10.3, 95% CI 2.0-52.6, P = 0.005, OR 18.4, 95% CI 2.2-155.3, P = 0.008, respectively). PIK3CA mutations were associated with a reduced risk of peritumoral edema (OR 0.2, 95% CI 0.04-0.8, P = 0.03)., Conclusions: Several genomic alterations in brain metastases are associated with MRI features including hemorrhage, cystic features, and edema. These results provide insight into tumor biology and patients at risk of developing these imaging features., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Anterior lumbar interbody fusion (ALIF) or transforaminal lumbar interbody fusion (TLIF) may be used to correct the lumbosacral fractional curve (LsFC) in de novo adult (thoraco) lumbar scoliosis. Yet, the relative benefits of ALIF and TLIF for LsFC correction remain largely undetermined., Purpose: To compare the currently available data comparing radiographic correction of the LsFC provided by ALIF and TLIF of LsFC in adult (thoraco)lumbar scoliosis., Methods: A systematic review was performed on original articles discussing fractional curve correction of lumbosacral spinal deformity (using search criteria: "lumbar" and "fractional curve"). Articles which discussed TLIF or ALIF for LsFC correction were presented and radiographic results for TLIF and ALIF were compared., Results: Thirty-one articles were returned in the original search criteria, with 7 articles included in the systematic review criteria. All 7 articles presented radiographic results using TLIF for LsFC correction. Three of these articles also discussed results for patients whose LsFC were treated with ALIFs; 2 articles directly compared TLIF and ALIF for LsFC correction. Level III and level IV evidence indicated ALIF as advantageous for reducing the coronal Cobb angle of the LsFC. There were mixed results on relative efficacy of ALIF and TLIF in the LsFC for restoration of adequate global coronal alignment., Conclusions: Limited level III and IV evidence suggests ALIF as advantageous for reducing the coronal Cobb angle of the LsFC in de novo adult (thoraco) lumbar scoliosis. Relative efficacy of ALIF and TLIF in the LsFC for restoration of global coronal alignment may be dictated by several factors, including directionality and magnitude of preoperative coronal deformity. Given the limited and low-quality evidence, additional research is warranted to determine the ideal interbody support strategies to address the LsFC in adult (thoraco) lumbar scoliosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Purpose: To assess recommendations for when adult spinal deformity (ASD) patients may return to athletic activities after surgery., Methods: A web-based survey was administered to members of AO Spine. The survey consisted of surgeon demographic information and questions asking when a patient undergoing a long thoracolumbar fusion (> 5 levels) with pelvic fixation for ASD would be allowed to resume unrestricted range of motion (ROM), non-contact sports, and contact sports postoperatively. Ordinal logistic regression was used to determine predictors for time to resume each activity., Results: One hundred twenty four members' responses were included for analysis. The majority of respondents would allow unrestricted ROM within 3 months postop (< 3 months: 81% vs > 3 months: 19%]. For when to return to non-contact sports, the most common responses were "2-3 months" (26.6%), "3-4 months" (26.6%), and "6-12 months" (18.5%). For when to return to contact sports, the majority advised > 4 months postop [> 4 months: "4-6 months" (19.2%), "6-12 months" (28.0%), " > 12 months" (28.8%) versus < 4 months: "1-2 months" (4.0%), "2-3 months" (1.6%), "3-4 months" (8.8%)]. 8.8% responded they would "never" allow resumption of contact sports., Conclusion: There was significant variation between surgeons' recommendations for resumption of unrestricted range of motion and sports following long fusion with pelvic fixation for ASD. An evidence-based approach to activity recommendations will require information on outcomes and complications., (© 2023. The Author(s).)

Objective: Maximal safe resection of gliomas near motor pathways is facilitated by intraoperative mapping. Here, the authors review their results with triple-modality asleep motor mapping with motor evoked potentials and bipolar and monopolar stimulation for cortical and subcortical mapping during glioma surgery in an expanded cohort., Methods: This was a retrospective analysis of patients who underwent resection of a perirolandic glioma near motor pathways. Clinical and neuromonitoring data were extracted from the electronic medical records for review. All patients with new or worsened postoperative motor deficits were followed for at least 6 months. Regression analyses were performed to assess factors associated with a persistent motor deficit., Results: Between January 2018 and December 2021, 160 operations were performed in 151 patients with perirolandic glioma. Sixty-four patients (40%) had preoperative motor deficits, and the median extent of resection was 98%. Overall, patients in 38 cases (23.8%) had new or worse immediate postoperative deficits by discharge, and persistent deficits by 6 months were seen in 6 cases (3.8%), all in patients with high-grade gliomas. There were no new persistent deficits in low-grade glioma patients (0%). The risk factors for a persistent deficit included an insular tumor component (OR 8.6, p = 0.01), preoperative motor weakness (OR 8.1, p = 0.03), intraoperative motor evoked potential (MEP) changes (OR 36.5, p < 0.0001), and peri-resection cavity ischemia (OR 7.5, p = 0.04). Most persistent deficits were attributable to ischemic injury despite structural preservation of the descending motor tracts. For patients with persistent motor deficits, there were 3 cases (50%) in which a change in MEP was noted but subsequent subcortical monopolar stimulation still elicited a response in the corresponding muscle groups, suggesting axonal activation distal to a point of injury., Conclusions: Asleep triple motor mapping results in a low rate of permanent deficits, especially for low-grade gliomas. Peri-resection cavity ischemia continues to be a significant risk factor for permanent deficit despite maintaining appropriate distance for subcortical tracts based on monopolar feedback.

Background: Pulsatile tinnitus (PT) can cause significant detriment to quality of life and may herald a life-threatening condition. Endovascular evaluation is the gold standard for the definitive diagnosis of PT and facilitates treatment. However, no large study has determined the distribution of causes and treatment outcomes of PT evaluated endovascularly., Methods: Consecutive patients evaluated at a multidisciplinary PT clinic from a single academic center were retrospectively reviewed. Patients with a suspected cerebrovascular etiology of PT based on clinical and/or non-invasive imaging, who were evaluated by endovascular techniques (arteriography, venography, manometry, and/or balloon test occlusion), were included in analysis. Baseline clinical features and treatment results by final etiology of PT were compared., Results: Of 552 patients referred for PT evaluation, 164 patients (29.7%) who underwent endovascular evaluation of PT were included. Mean (±SD) age at first clinical evaluation was 54.3±14.1 years (range 25-89 years); 111 patients (67.7%) were female. PT causes were 75.6% vascular and 24.4% non-vascular. Arteriovenous shunting lesions caused 20.7% of cases, venous etiologies 48.2%, and arterial etiologies 6.7%. Of patients with a shunting lesion treated with endovascular embolization, 96.9% had lasting significant improvement or resolution in PT. Endovascular stenting for venous sinus stenosis gave 84.6% of patients lasting improvement or resolution in PT. Arterial and non-vascular PT had fewer patients treated endovascularly and less improvement in PT symptoms., Conclusion: PT with a suspected vascular cause is most often attributable to venous etiologies. PT caused by arteriovenous shunting or venous sinus stenosis may be effectively treated endovascularly., Competing Interests: Competing interests: MRA: Board member: Mind Rhythm; Consultancy: Stryker, Neurovascular, Covidien, MicroVention, Comments: Pipeline proctor for Covidien and PHIL DSMB for MicroVention; Patents (planned, pending or issued): Cerebral venous sinus stent, Comments: provisional patent serial number 62/984,549. KHN: Consultancy: Stryker Neurovascular, Imperative Care. All other authors: No relevant competing interests., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Intraventricular meningiomas (IVMs) of the lateral ventricle are rare tumors that present surgical challenges because of their deep location. Visual field deficits (VFDs) are one risk associated with these tumors and their treatment. VFDs may be present preoperatively due to the tumor and mass effect (tumor VFDs) or may develop postoperatively due to the surgical approach (surgical VFDs). This institutional series aimed to review surgical outcomes following resection of IVMs, with a focus on VFDs., Methods: Patients who received IVM resection at one academic institution between the years 1996 and 2021 were retrospectively reviewed. Diffusion tensor imaging (DTI) reconstructions of the optic radiations around the tumor were performed from preoperative IVM imaging. The VFD course and resolution were documented., Results: Thirty-two adult patients underwent IVM resection, with gross-total resection in 30 patients (93.8%). Preoperatively, tumor VFDs were present in 6 patients, resolving after surgery in 5 patients. Five other patients (without preoperative VFD) had new persistent surgical VFDs postoperatively (5/32, 15.6%) that persisted to the most recent follow-up. Of the 5 patients with persistent surgical VFDs, 4 received a transtemporal approach and 1 received a transparietal approach, and all these deficits occurred prior to regular use of DTI in preoperative imaging., Conclusions: New surgical VFDs are a common neurological deficit after IVM resection. Preoperative DTI may demonstrate distortion of the optic radiations around the tumor, thus revealing safe operative corridors to prevent surgical VFDs.

Objective: To compare in-hospital and 30-day postoperative complications for lumbar spine operations with and without use of computer-assisted navigation., Methods: Patients who underwent 1-level to 3-level lumbar spinal instrumentation and fusions 2011 to 2014 were identified in the American College of Surgeons National Surgical Quality Improvement Program database. Emergent procedures and patients aged younger than 18 years were excluded. Patients whose surgery involved the use of computer-assisted navigation were propensity score matched 1:4 based on preoperative demographics and comorbidities to operations without the use of navigation. Multivariate analysis was done to compare postoperative complications., Results: In total, 8,500 patients (average age: 60.7 ± 12.9, male 3,866, female 4,634) were analyzed (1,700 navigation, 6,800 Non-Navigated). Operations with navigation had significantly fewer overall complications (24% vs. 27%, P = 0.008; odds ratio [OR] = 0.83; CI = 0.73 to 0.95), fewer minor complications (20% vs. 24%, P = 0.002; OR = 0.80; CI = 0.70 to 0.91), fewer blood transfusions (17% v. 20%, P = 0.013; OR = 0.82; CI = 0.71 to 0.95), more wound dehiscences (0.4% vs. 0.8%, P = 0.022; OR = 2.16; CI = 1.12,4.19), and shorter average lengths of hospital stays (4.8 ± 4.8 vs. 5.1 ± 5.8 days, P = 0.01). Operations with computer navigation had significantly longer average surgical times (247 ± 129 vs 221 ± 115 minutes, P < 0.001). No significant differences were observed in 30-day revision rates, readmissions, and mortality., Conclusion: Although use of computer-assisted navigation in short-segment lumbar spine fusions (1 to 3 levels) did not decrease revision rates for screw misplacement within 30 days postoperatively, it independently reduced the frequency of blood transfusions and minor complications and decreased hospital lengths of stay compared with operations without navigation. These benefits came at the expense of increased surgical times and wound dehiscences within 30 days postoperatively. Given the inherent limitations of large national databases, these results warrant confirmation through prospective, multicenter investigations., (Copyright © 2023 by the American Academy of Orthopaedic Surgeons.)

Objective: The aim of this study was to investigate associations between genomic alterations in resected brain metastases and rapid local and distant CNS recurrence identified at the time of postoperative adjuvant radiosurgery., Methods: This was a retrospective study on patients who underwent resection of intracranial brain metastases. Next-generation sequencing of more than 500 coding genes was performed on brain metastasis specimens. Postoperative and preradiosurgery MR images were compared to identify rapid recurrence. Genomic data were associated with rapid local and distant CNS recurrence of brain metastases using nominal regression analyses., Results: The cohort contained 92 patients with 92 brain metastases. Thirteen (14.1%) patients had a rapid local recurrence, and 64 (69.6%) patients had rapid distant CNS progression by the time of postoperative adjuvant radiosurgery, which occurred in a median time of 25 days (range 3-85 days) from surgery. RB1 and CTNNB1 mutations were seen in 8.7% and 9.8% of the cohort, respectively, and were associated with a significantly higher risk of rapid local recurrence (RB1: OR 13.6, 95% CI 2.0-92.39, p = 0.008; and CTNNB1: OR 11.97, 95% CI 2.25-63.78, p = 0.004) on multivariate analysis. No genes were found to be associated with rapid distant CNS progression. However, the presence of extracranial disease was significantly associated with a higher risk of rapid distant recurrence on multivariate analysis (OR 4.06, 95% CI 1.08-15.34, p = 0.039)., Conclusions: Genomic alterations in RB1 or CTNNB1 were associated with a significantly higher risk of rapid recurrence at the resection site. Although no genomic alterations were associated with rapid distant recurrence, having active extracranial disease was a risk factor for new lesions by the time of adjuvant radiotherapy after resection.

Objective: Seizures are common and significantly disabling for patients with brain metastases (BMs). Although resection can provide seizure control, a subset of patients with BMs may continue to suffer seizures postoperatively. Genomic BM characteristics may influence which patients are at risk for postoperative seizures. This work explores correlations between genomic alterations and risk of postoperative seizures following BM resection., Methods: All patients underwent BM resection at a single institution, with available clinical and sequencing data on more than 500 oncogenes. Clinical seizures were documented pre- and postoperatively. A random forest machine learning classification was used to determine candidate genomic alterations associated with postoperative seizures, and clinical and top genomic variables were correlated with postoperative seizures by using Cox proportional hazards models., Results: There were 112 patients with BMs who underwent 114 surgeries and had at least 1 month of postoperative follow-up. Seizures occurred preoperatively in 26 (22.8%) patients and postoperatively in 25 (21.9%). The Engel classification achieved at 6 months for those with preoperative seizures was class I in 13 (50%); class II in 6 (23.1%); class III in 5 (19.2%), and class IV in 2 (7.7%). In those with postoperative seizures, only 8 (32.0%) had seizures preoperatively, and preoperative seizures were not a significant predictor of postoperative seizures (HR 1.84; 95% CI 0.79-4.37; p = 0.156). On random forest classification and multivariate Cox analysis controlling for factors including recurrence, extent of resection, and number of BMs, CDKN2A alterations were associated with postoperative seizures (HR 3.22; 95% CI 1.27-8.16; p = 0.014). Melanoma BMs were associated with higher risk of postoperative seizures compared with all other primary malignancies (HR 5.23; 95% CI 1.37-19.98; p = 0.016). Of 39 BMs with CDKN2A alteration, 35.9% (14/39) had postoperative seizures, compared to 14.7% (11/75) without CDKN2A alteration. The overall rate of postoperative seizures in melanoma BMs was 42.9% (15/35), compared with 12.7% (10/79) for all other primary malignancies., Conclusions: CDKN2A alterations and melanoma primary malignancy are associated with increased postoperative seizure risk following resection of BMs. These results may help guide postoperative seizure prophylaxis in patients undergoing resection of BMs.

Objective: The relationship between brain metastasis resection and risk of nodular leptomeningeal disease (nLMD) is unclear. This study examined genomic alterations found in brain metastases with the aim of identifying alterations associated with postoperative nLMD in the context of clinical and treatment factors., Methods: A retrospective, single-center study was conducted on patients who underwent resection of brain metastases between 2014 and 2022 and had clinical and genomic data available. Postoperative nLMD was the primary endpoint of interest. Targeted next-generation sequencing of > 500 oncogenes was performed in brain metastases. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with nLMD., Results: The cohort comprised 101 patients with tumors originating from multiple cancer types. There were 15 patients with nLMD (14.9% of the cohort) with a median time from surgery to nLMD diagnosis of 8.2 months. Two supervised machine learning algorithms consistently identified CDKN2A/B codeletion and ERBB2 amplification as the top predictors associated with postoperative nLMD across all cancer types. In a multivariate Cox proportional hazards analysis including clinical factors and genomic alterations observed in the cohort, tumor volume (× 10 cm3; HR 1.2, 95% CI 1.01-1.5; p = 0.04), CDKN2A/B codeletion (HR 5.3, 95% CI 1.7-16.9; p = 0.004), and ERBB2 amplification (HR 3.9, 95% CI 1.1-14.4; p = 0.04) were associated with a decreased time to postoperative nLMD., Conclusions: In addition to increased resected tumor volume, ERBB2 amplification and CDKN2A/B deletion were independently associated with an increased risk of postoperative nLMD across multiple cancer types. Additional work is needed to determine if targeted therapy decreases this risk in the postoperative setting.

Introduction: The purpose of this study is to provide a state-of-the-art review regarding risk factors for perioperative complications in adult spinal deformity (ASD) surgery. The review includes levels of evidence for risk factors associated with complications in ASD surgery., Methods: Using the PubMed database, we searched for complications, risk factors, and adult spinal deformity. The included publications were assessed for level of evidence as described in clinical practice guidelines published by the North American Spine Society, with summary statements generated for each risk factor (Bono et al. in Spine J 9:1046-1051, 2009)., Results: Frailty had good evidence (Grade A) as a risk for complications in ASD patients. Fair evidence (Grade B) was assigned for bone quality, smoking, hyperglycemia and diabetes, nutritional status, immunosuppression/steroid use, cardiovascular disease, pulmonary disease, and renal disease. Indeterminate evidence (Grade I) was assigned for pre-operative cognitive function, mental health, social support, and opioid utilization., Conclusions: Identification of risk factors for perioperative complications in ASD surgery is a priority for empowering informed choices for patients and surgeons and managing patient expectations. Risk factors with grade A and B evidence should be identified prior to elective surgery and modified to reduce the risk of perioperative complications., (© 2023. The Author(s).)

Background Context: Postoperative recovery after adult spinal deformity (ASD) operations is arduous, fraught with complications, and often requires extended hospital stays. A need exists for a method to rapidly predict patients at risk for extended length of stay (eLOS) in the preoperative setting., Purpose: To develop a machine learning model to preoperatively estimate the likelihood of eLOS following elective multi-level lumbar/thoracolumbar spinal instrumented fusions (≥3 segments) for ASD., Study Design/setting: Retrospectively from a state-level inpatient database hosted by the Health care cost and Utilization Project., Patient Sample: Of 8,866 patients of age ≥50 with ASD undergoing elective lumbar or thoracolumbar multilevel instrumented fusions., Outcome Measures: The primary outcome was eLOS (>7 days)., Methods: Predictive variables consisted of demographics, comorbidities, and operative information. Significant variables from univariate and multivariate analyses were used to develop a logistic regression-based predictive model that use six predictors. Model accuracy was assessed through area under the curve (AUC), sensitivity, and specificity., Results: Of 8,866 patients met inclusion criteria. A saturated logistic model with all significant variables from multivariate analysis was developed (AUC=0.77), followed by generation of a simplified logistic model through stepwise logistic regression (AUC=0.76). Peak AUC was reached with inclusion of six selected predictors (combined anterior and posterior approach, surgery to both lumbar and thoracic regions, ≥8 level fusion, malnutrition, congestive heart failure, and academic institution). A cutoff of 0.18 for eLOS yielded a sensitivity of 77% and specificity of 68%., Conclusions: This predictive model can facilitate identification of adults at risk for eLOS following elective multilevel lumbar/thoracolumbar spinal instrumented fusions for ASD. With a fair diagnostic accuracy, the predictive calculator will ideally enable clinicians to improve preoperative planning, guide patient expectations, enable optimization of modifiable risk factors, facilitate appropriate discharge planning, stratify financial risk, and accurately identify patients who may represent high-cost outliers. Future prospective studies that validate this risk assessment tool on external datasets would be valuable., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: While genetic alterations in brain metastases (BMs) have been previously explored, there are limited data examining their association with recurrence after surgical resection. This study aimed to identify genetic alterations within BMs associated with CNS recurrence after surgery across multiple cancer types., Methods: A retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical and gene sequencing data available. Local and remote CNS recurrence were the primary study outcomes. Next-generation sequencing of the coding regions in over 500 oncogenes was performed in brain metastasis specimens. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with CNS recurrence., Results: A total of 90 patients undergoing resection of 91 BMs composed the cohort. Genes most frequently mutated in the cohort included TP53 (64%), CDKN2A (37%), TERT (29%), CDKN2B (23%), NF1 (14%), KRAS (14%), and PTEN (13%), all of which occurred across multiple cancer types. CDKN2A/B co-deletion was seen in 21 (23.1%) brain metastases across multiple cancer types. In multivariate Cox proportional hazard analyses including patient, tumor, and treatment factors, CDKN2A/B co-deletion in the brain metastasis was associated with increased risk of local (HR 4.07, 95% CI 1.32-12.54, P = 0.014) and remote (HR 2.28, 95% CI 1.11-4.69, P = 0.025) CNS progression. Median survival and length of follow-up were not different based on CDKN2A/B mutation status., Conclusions: CDKN2A/B co-deletion detected in BMs is associated with increased CNS recurrence after surgical resection. Additional work is needed to determine whether more aggressive treatment in patients with this mutation may improve outcomes., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Objective: Resection of brain metastases (BMs) may be associated with increased risk of leptomeningeal disease (LMD). This study examined rates and predictors of LMD, including imaging subtypes, in patients who underwent resection of a BM followed by postoperative radiation., Methods: A retrospective, single-center study was conducted examining overall LMD, classic LMD (cLMD), and nodular LMD (nLMD) risk. Logistic regression, Cox proportional hazards, and random forest analyses were performed to identify risk factors associated with LMD., Results: Of the 217 patients in the cohort, 47 (21.7%) developed postoperative LMD, with 19 cases (8.8%) of cLMD and 28 cases (12.9%) of nLMD. Six-, 12-, and 24-month LMD-free survival rates were 92.3%, 85.6%, and 71.4%, respectively. Patients with cLMD had worse survival outcomes from the date of LMD diagnosis compared with nLMD (median 2.4 vs 6.9 months, p = 0.02, log-rank test). Cox proportional hazards analysis identified cerebellar/insular/occipital location (hazard ratio [HR] 3.25, 95% confidence interval [CI] 1.73-6.11, p = 0.0003), absence of extracranial disease (HR 2.49, 95% CI 1.27-4.88, p = 0.008), and ventricle contact (HR 2.82, 95% CI 1.5-5.3, p = 0.001) to be associated with postoperative LMD. A predictive model using random forest analysis with an area under the receiver operating characteristic curve of 0.87 in a test cohort identified tumor location, systemic disease status, and tumor volume as the most important factors associated with LMD., Conclusions: Tumor location, absence of extracranial disease at the time of surgery, ventricle contact, and increased tumor volume were associated with LMD. Further work is needed to determine whether escalating therapies in patients at risk of LMD prevents disease dissemination.

Purpose: To develop a model for factors predictive of Post-Acute Care Facility (PACF) discharge in adult patients undergoing elective multi-level (≥ 3 segments) lumbar/thoracolumbar spinal instrumented fusions., Methods: The State Inpatient Databases acquired from the Healthcare Cost and Utilization Project from 2005 to 2013 were queried for adult patients who underwent elective multi-level thoracolumbar fusions for spinal deformity. Outcome variables were classified as discharge to home or PACF. Predictive variables included demographic, pre-operative, and operative factors. Univariate and multivariate logistic regression analyses informed development of a logistic regression-based predictive model using seven selected variables. Performance metrics included area under the curve (AUC), sensitivity, and specificity., Results: Included for analysis were 8866 patients. The logistic model including significant variables from multivariate analysis yielded an AUC of 0.75. Stepwise logistic regression was used to simplify the model and assess number of variables needed to reach peak AUC, which included seven selected predictors (insurance, interspaces fused, gender, age, surgical region, CCI, and revision surgery) and had an AUC of 0.74. Model cut-off for predictive PACF discharge was 0.41, yielding a sensitivity of 75% and specificity of 59%., Conclusions: The seven variables associated significantly with PACF discharge (age > 60, female gender, non-private insurance, primary operations, instrumented fusion involving 8+ interspaces, thoracolumbar region, and higher CCI scores) may aid in identification of adults at risk for discharge to a PACF following elective multi-level lumbar/thoracolumbar spinal fusions for spinal deformity. This may in turn inform discharge planning and expectation management., (© 2022. The Author(s).)

Background: Shunting is an established treatment for hydrocephalus, yet reports on shunt outcomes for nonbacterial infection (NBI) hydrocephalus are limited. Furthermore, comparison of mechanisms and rates of failure for shunted NBI hydrocephalus versus more typical etiologies remains undetermined., Methods: Patients who underwent shunting for hydrocephalus at 2 centers (1995-2020) were included. Indications for shunting were grouped as "typical" (congenital, posthemorrhagic, normal pressure hydrocephalus, malignancy-related, trauma, and idiopathic) and NBI hydrocephalus (coccidioidomycosis, cryptococcosis, and neurocysticercosis). Rates of shunt malfunction were compared., Results: There were 261 patients shunted for typical hydrocephalus (48.7% male; age = 50.7 ± 21.7) and 93 patients for NBI hydrocephalus (72.0% male; age = 41.8 ± 13.2). For patients with typical hydrocephalus, 29.5% required ≥1 shunt revision, compared with 64.5% with NBI hydrocephalus (P < 1E-5). Of those with malfunction, NBI shunts required more revision operations (median = 3.0; max = 21) than typical shunts (median = 2.0; max = 6; P < 0.05). The censored median time to shunt failure for NBI hydrocephalus was 26.9 months and was not reached for typical etiologies by 180 months. Multivariate analysis showed shunts for NBI hydrocephalus were significantly more likely to fail (hazard ratio = 2.25; 95% confidence interval = 1.58-3.19). A distal pseudocyst was implicated in 30.0% and 2.6% of shunt failures for NBI and typical hydrocephalus, respectively (P < 1E-5). Sixteen (26.7%) NBI shunt failures required revision to lower-resistance systems compared to 6 (7.8%) typical failures (P < 0.05)., Conclusions: Shunts placed for hydrocephalus secondary to nonbacterial infections are complicated by significantly higher rates of malfunction. These patients are prone to develop distal abdominal pseudocysts and often require revision to low-resistance systems., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Meningiomas are the most common primary intracranial tumor, and resection is a mainstay of treatment. It is unclear what duration of imaging follow-up is reasonable for WHO grade I meningiomas undergoing complete resection. This study examined recurrence rates, timing of recurrence, and risk factors for recurrence in patients undergoing a complete resection (as defined by both postoperative MRI and intraoperative impression) of WHO grade I meningiomas., Methods: The authors conducted a retrospective, single-center study examining recurrence risk for adult patients with a single intracranial meningioma that underwent complete resection. Uni- and multivariate nominal logistic regression and Cox proportional hazards analyses were performed to identify variables associated with recurrence and time to recurrence. Two supervised machine learning algorithms were then implemented to confirm factors within the cohort that were associated with recurrence., Results: The cohort consisted of 823 patients who met inclusion criteria, and 56 patients (6.8%) had recurrence on imaging follow-up. The median age of the cohort was 56 years, and 77.4% of patients were female. The median duration of head imaging follow-up for the entire cohort was 2.7 years, but for the subgroup of patients who had a recurrence, the median follow-up was 10.1 years. Estimated 1-, 5-, 10-, and 15-year recurrence-free survival rates were 99.8% (95% confidence interval [CI] 98.8%-99.9%), 91.0% (95% CI 87.7%-93.6%), 83.6% (95% CI 78.6%-87.6%), and 77.3% (95% CI 69.7%-83.4%), respectively, for the entire cohort. On multivariate analysis, MIB-1 index (odds ratio [OR] per 1% increase: 1.34, 95% CI 1.13-1.58, p = 0.0003) and follow-up duration (OR per year: 1.12, 95% CI 1.03-1.21, p = 0.012) were both associated with recurrence. Gradient-boosted decision tree and random forest analyses both identified MIB-1 index as the main factor associated with recurrence, aside from length of imaging follow-up. For tumors with an MIB-1 index < 8, recurrences were documented up to 8 years after surgery. For tumors with an MIB-1 index ≥ 8, recurrences were documented up to 12 years following surgery., Conclusions: Long-term imaging follow-up is important even after a complete resection of a meningioma. Higher MIB-1 labeling index is associated with greater risk of recurrence. Imaging screening for at least 8 years in patients with an MIB-1 index < 8 and at least 12 years for those with an MIB-1 index ≥ 8 may be needed to detect long-term recurrences.

Background: Despite reports on the efficacy of checkpoint inhibitor (CPI) immunotherapies for metastatic cancers, there are limited data on the effectiveness of surgery for brain metastases (BMs) that have progressed after previous CPI treatment. We sought to evaluate surgical outcomes for patients undergoing BM resection after failing CPI immunotherapy., Methods: A single-center series of patients with BM that had progressed after previous CPI treatment and who underwent surgery was retrospectively reviewed. Outcomes of interest included local tumor progression, leptomeningeal dissemination, and overall survival. Cox proportional hazard models were applied to determine factors associated with outcomes of interest., Results: Over a 16-year period, 26 patients underwent resection of 32 BMs at a median of 1.2 months (range, 2 days-41.1 months) from their last CPI dose. Median censored survival was 7.6 months from surgery and was shorter than the survival of patients without previous CPI exposure (21.9 months; log-rank P = 0.001). Four BMs had local central nervous system progression (16%), and 75% of procedures were associated with distant central nervous system progression within a median time of 3.3 months. Leptomeningeal disease developed after 33.3% of surgeries. Increased time from first BM diagnosis to surgery was associated with increased risk of leptomeningeal disease (hazard ratio by month, 1.07; 95% confidence interval, 1.01-1.14; P = 0.03)., Conclusions: Patients who require BM resection after previous CPI treatment have a poor overall prognosis compared with patients without previous CPI exposure. Although local control rates are acceptable, these patients are at high risk for developing distant progression and leptomeningeal disease postoperatively., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study wasto evaluate cause-specific 5-year revision rates and risk factors for revision after elective multilevel lumbar instrumented fusion in older patients., Methods: Older patients (>60 years) who underwent elective multilevel (3+) lumbar instrumented fusions were identified in Healthcare Cost and Utilization Project state inpatient databases and followed for 5 years for revision operations because of mechanical failure, degenerative disease (DD), infection, postlaminectomy syndrome, and stenosis. Cox proportional hazards multivariate analyses were conducted to determine risk factors associated with revision for each diagnostic cause., Results: The cohort included 5,636 patients (female-3,285; average age-71.6 years). Most of the operations were 3 to 7 levels (97.4%), and the mean length of stay was 5.4 days. The overall 5-year revision rate was 16.5% with predominant etiologies of DD (50.7%), mechanical failure (32.2%), and stenosis (8.0%). The revision procedure at the index operation was associated with an increased revision risk for DD (hazards ratio [HR] = 1.59, 95% confidence interval [CI], 1.29 to 1.98, P < 0.001) and mechanical failure (HR = 1.56, 95% CI, 1.19 to 2.04, P = 0.020). Male sex was associated with a significantly reduced revision risk for DD (HR = 0.75, 95% CI, 0.62 to 0.91, P = 0.04). Age, race, and number of comorbidities had no notable effect on the overall or cause-specific risk of revision., Discussion: In this large database analysis, DD and mechanical failure were the most common etiologies comprising a 5-year revision rate of 16.5% after elective multilevel lumbar instrumented fusion in older patients. Revision operations and female patients carried the strongest risks for revision., (Copyright © 2022 by the American Academy of Orthopaedic Surgeons.)

Background: There are numerous atypical lesions of the sellar and suprasellar region that are often mistaken for pituitary adenomas. It is important to consider rare mimics of more common pathologies in this region., Observations: The authors detail the case of a 37-year-old woman with hypopituitarism who was found to have an atypical sellar mass with slow growth on interval imaging. The lesion was debulked via a microscopic endonasal transsphenoidal approach and found to be a calcifying pseudoneoplasm of the neuraxis (CAPNON)., Lessons: CAPNON is a rare disease entity that may affect the sellar region. CAPNON should be on the differential diagnosis for sellar masses that are associated with T1 and T2 hypointensity on magnetic resonance imaging with minimal enhancement. Although CAPNON is not at risk for malignant progression, these benign lesions can continue to grow after a subtotal resection and require follow-up.

Introduction: Adjacent segment disease (ASD) of the cervical spine is a common disabling phenomenon that often requires surgical intervention. The goal of this study was to evaluate the economic impact of revision operations for cervical ASD., Methods: Consecutive adults who underwent revision cervical spine surgery for ASD at a single institution between 2014 and 2017 were retrospectively reviewed. Direct costs were identified from medical billing data and calculated for each revision surgery for ASD. Incomplete cost data for revision operations were used as a criterion for exclusion. Cost data were stratified based on the approach of the index and revision operations., Results: Eighty-five patients (average age 57 ± 10 years) underwent revisions for cervical ASD, which summed to $2 million (average $23,702). Revisions consisted of 45 anterior operations (anterior cervical diskectomy and fusion, 34; corpectomy, 10; and cervical disk arthroplasty, 1), 32 posterior operations (posterior cervical fusion, 14; foraminotomy, 14; and laminoplasty, 4), and 8 circumferential operations. Circumferential revisions had notably higher average direct costs ($57,376) than single approaches (anterior, $20,084 and posterior, $20,371). Of posterior revisions, foraminotomies had the lowest average direct costs ($5,389), whereas posterior cervical fusion had the highest average direct costs ($35,950). Of anterior revisions, corpectomies ($30,265) had notably greater average direct costs than anterior cervical diskectomy and fusion ($17,514). Costs were not notably different for revision approaches based on the index operations' approach., Discussion: Revision operations for cervical ASD are highly heterogeneous and associated with an average direct cost of $27,702. Over 3 years, revisions for 85 patients with cervical ASD represented a notable economic expense (greater than $2.0 million)., Data Availability: Deidentified data may be provided by request to the corresponding author., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Early diagnosis of psoriatic arthritis (PSA) is important for successful therapeutic intervention but currently remains challenging due, in part, to the scarcity of non-invasive biomarkers. In this study, we performed single cell profiling of transcriptome and cell surface protein expression to compare the peripheral blood immunocyte populations of individuals with PSA, individuals with cutaneous psoriasis (PSO) alone, and healthy individuals. We identified genes and proteins differentially expressed between PSA, PSO, and healthy subjects across 30 immune cell types and observed that some cell types, as well as specific phenotypic subsets of cells, differed in abundance between these cohorts. Cell type-specific gene and protein expression differences between PSA, PSO, and healthy groups, along with 200 previously published genetic risk factors for PSA, were further used to perform machine learning classification, with the best models achieving AUROC ≥ 0.87 when either classifying subjects among the three groups or specifically distinguishing PSA from PSO. Our findings thus expand the repertoire of gene, protein, and cellular biomarkers relevant to PSA and demonstrate the utility of machine learning-based diagnostics for this disease., Competing Interests: Author WL has received funding from Abbvie, Amgen, Janssen, Leo, Novartis, Pfizer, Regeneron, and TRex Bio. Author CY is a Scientific Advisory Board member for and holds equity in Related Sciences and ImmunAI, a consultant for and holds equity in Maze Therapeutics, and a consultant for TReX Bio. Author CY has received funding from Chan Zuckerberg Initiative, Chan Zuckerberg Biohub, and Genentech. Author LG has received funding from Novartis, Pfizer, UCB, AbbVie, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Kumar, Hong, Huang, Paez, Castillo, Calvo, Chang, Cummins, Chung, Yeroushalmi, Bartholomew, Hakimi, Ye, Bhutani, Matloubian, Gensler and Liao.)

Background and Purpose: Pulsatile tinnitus (PT) is the subjective sensation of a pulse-synchronous sound, most often due to a cerebrovascular etiology. PT can severely impact quality of life and may indicate a life-threatening process, yet a timely and accurate diagnosis can often lead to effective treatment. Clinical assessment with a history and physical examination can often suggest a diagnosis for PT, but is rarely definitive. Therefore, PT should be evaluated with a comprehensive and targeted radiographic imaging protocol. MR imaging provides a safe and effective means to evaluate PT. Specific MR sequences may be used to highlight different elements of cerebrovascular anatomy and physiology. However, routine MR evaluation of PT must comply with economic and practical constraints, while effectively capturing both common and rarer, life-threatening etiologies of PT., Methods: In this state-of-the-art review, we describe our institutional MR protocol for evaluating PT., Results: This protocol includes the following dedicated sequences: time-of-flight magnetic resonance angiography; arterial spin labeling; spoiled gradient recalled acquisition in the steady state; time-resolved imaging of contrast kinetics; diffusion weighted imaging, and 3-dimensional fluid-attenuated inversion recovery., Conclusions: We describe the physiologic and clinical rationale for including each MR sequence in a comprehensive PT imaging protocol, and detail the role of MR within the broader evaluation of PT, from clinical presentation to treatment., (© 2021 American Society of Neuroimaging.)

Background: Although overall survival (OS) has improved in patients with brain metastases (BMs), control of recurrent BMs remains a therapeutic challenge. Salvage surgery may achieve acceptable control rates in the setting of progression after previous stereotactic radiosurgery (SRS), yet it remains a question how additional adjuvant therapies may affect outcomes and how patient selection for salvage surgery may be optimized., Methods: Patients receiving salvage surgery for BM progression after previous SRS were retrospectively reviewed from a single center. Outcomes of interest included local tumor progression, leptomeningeal dissemination, and OS. Cox proportional hazard models and nominal logistic regression were applied to determine factors associated with outcomes of interest., Results: A total of 43 patients with 50 BMs were included. After salvage surgery, local progression was observed for 17 BMs (34%), leptomeningeal dissemination was observed in 17 patients (39.5%), and censored median OS was 17.9 months. On multivariate analysis, use of brachytherapy was associated with improved local control (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04-0.6; P = 0.008). For patients treated with SRS ≥4.5 months before salvage surgery, both brachytherapy (HR, 0.07; 95% CI, 0.01-0.39; P = 0.002) and postoperative adjuvant SRS (HR, 0.14; 95% CI, 0.02-1.00; P = 0.05) were associated with improved local control compared with no adjuvant radiation therapy. Presence of extracranial malignancy (HR, 6.70; 95% CI, 2.58-17.42; P < 0.0001) was associated with shorter survival. Graded prognostic assessment underestimated survival in 79.1% of patients, with a mean difference of 18.9 months between graded prognostic assessment-estimated and actual OS., Conclusions: In properly selected patients, salvage surgery may be an appropriate therapy for BM progression after previous SRS. Adjuvant brachytherapy and repeat SRS can offer significant benefit for local control with salvage resection., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The IL-17A inhibitor secukinumab is efficacious for the treatment of psoriasis. To better understand its mechanism of action, we investigated its impact on psoriatic lesions from 15 patients with moderate-to-severe plaque psoriasis undergoing secukinumab treatment. We characterized the longitudinal transcriptomic changes of whole lesional skin tissue as well as cutaneous CD4 + and CD8 + T effector cells and CD4 + T regulatory cells across 12 weeks of treatment. Secukinumab was clinically effective and reduced disease-associated overexpression of IL17A , IL17F, IL23A, IL23R , and IFNG in whole tissue as soon as 2 weeks after initiation of treatment. IL17A overexpression in T-cell subsets, primarily CD8 + T cells, was also reduced. Although secukinumab treatment resolved 89‒97% of psoriasis-associated expression differences in bulk tissue and T-cell subsets by week 12 of treatment, we observed expression differences involved in IFN signaling and metallothionein synthesis that remained unresolved at this time point as well as potential treatment-associated expression differences involved in IL-15 signaling. These changes were accompanied by shifts in broader immune cell composition on the basis of deconvolution of RNA-sequencing data. In conclusion, our study reveals several phenotypic and cellular changes within the lesion that underlie clinical improvement from secukinumab., (© 2021 The Authors.)

Background: Brain sensing devices are approved today for Parkinson's, essential tremor, and epilepsy therapies. Clinical decisions for implants are often influenced by the premise that patients will benefit from using sensing technology. However, artifacts, such as ECG contamination, can render such treatments unreliable. Therefore, clinicians need to understand how surgical decisions may affect artifact probability., Objectives: Investigate neural signal contamination with ECG activity in sensing enabled neurostimulation systems, and in particular clinical choices such as implant location that impact signal fidelity., Methods: Electric field modeling and empirical signals from 85 patients were used to investigate the relationship between implant location and ECG contamination., Results: The impact on neural recordings depends on the difference between ECG signal and noise floor of the electrophysiological recording. Empirically, we demonstrate that severe ECG contamination was more than 3.2x higher in left-sided subclavicular implants (48.3%), when compared to right-sided implants (15.3%). Cranial implants did not show ECG contamination., Conclusions: Given the relative frequency of corrupted neural signals, we conclude that implant location will impact the ability of brain sensing devices to be used for "closed-loop" algorithms. Clinical adjustments such as implant location can significantly affect signal integrity and need consideration., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Many adaptative deep brain stimulation (DBS) paradigms rely upon the ability to sense neural signatures of specific clinical signs or symptoms in order to modulate therapeutic stimulation. In first-generation bidirectional neurostimulators, the ability to sense neural signals during active stimulation was often limited by artifact. Newer devices, with improved design specifications for sensing, have recently been developed and are now clinically available., Objective: To compare the sensing capabilities of the first-generation Medtronic PC + S and second-generation Percept PC neurostimulators within a single patient., Methods: A 42-year-old man with Parkinson's disease was initially implanted with left STN DBS leads connected to a PC + S implantable pulse generator. Four years later, the PC + S was replaced with the Percept PC. Local field potential (LFP) signals were recorded, both with stimulation OFF and ON, at multiple timepoints with each device and compared. Offline processing of time series data included artifact removal using digital filtering and template subtraction, before subsequent spectral analysis. With Percept PC, embedded processing of spectral power within a narrow frequency band was also utilized., Results: In the absence of stimulation, both devices demonstrated a peak in the beta range (approximately 20 Hz), which was stable throughout the 4-year period. Similar to previous reports, recordings with the PC + S during active stimulation demonstrated significant stimulation artifact, limiting the ability to recover meaningful LFP signal. In contrast, the Percept PC, using the same electrodes and stimulation settings, produced time series data during stimulation with spectral analysis revealing a peak in the beta-band. Online analysis by the Percept demonstrated a reduction in beta-band activity with increasing stimulation amplitude., Conclusion: This report highlights recent advances in implantable neurostimulator technology for DBS, demonstrating improvements in sensing capabilities during active stimulation between first- and second-generation devices. The ability to reliably sense during stimulation is an important step toward both the clinical implementation of adaptive algorithms and the further investigation into the neurophysiology underlying movement disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cummins, Kochanski, Gilron, Swann, Little, Hammer and Starr.)

Lipopolysaccharides (LPSs) are vital components of the outer membrane of Gram-negative bacteria, and they act as extremely strong stimulators of innate immunity in diverse eukaryotic species. The primary immunostimulatory center of the LPS molecule is lipid A, a disaccharide-bound lipophilic domain. Considering the broad diversity in bacterial species, there are variations in the lipid A structures and their immunogenic potencies. In this work, we model the lipid A structures of eight commensal or human pathogenic bacterial species: Helicobacter pylori, Porphyromonas gingivalis, Bacteroides fragilis, Bordetella pertussis, Chlamydia trachomatis, Campylobacter jejuni, Neisseria meningitidis, and Salmonella minnesota. The membrane properties of these bacterial species were characterized and compared using molecular simulations. The structure-property relationships that emerge from this lipid A molecular library highlight the roles of acyl chain lengths, number of chains, phosphorylation state, membrane composition, and counterion charge in regulating the phase transition temperature of the membrane, diffusion coefficient of the lipids, and membrane thickness. The molecular and structural insights provided reveal the diversity in bacterial outer membrane lipids and their contribution to human disease and immunity.

Causal inference is a fundamental component of cognition and perception. Probabilistic theories of causal judgment (most notably causal Bayes networks) derive causal judgments using metrics that integrate contingency information. But human estimates typically diverge from these normative predictions. This is because human causal power judgments are typically strongly influenced by beliefs concerning underlying causal mechanisms, and because of the way knowledge is retrieved from human memory during the judgment process. Neuroimaging studies indicate that the brain distinguishes causal events from mere covariation, and also distinguishes between perceived and inferred causality. Areas involved in error prediction are also activated, implying automatic activation of possible exception cases during causal decision-making.

People consider alternative causes when deciding whether a cause is responsible for an effect (diagnostic inference) but appear to neglect them when deciding whether an effect will occur (predictive inference). Five experiments were conducted to test a 2-part explanation of this phenomenon: namely, (a) that people interpret standard predictive queries as requests to estimate the probability of the effect in the presence of the cause alone, which renders alternative causes irrelevant, and (b) that the impact of disablers (inhibitory causes) on predictive judgments is underestimated, and this underestimation is wrongly interpreted as cause neglect. Experiment 1 showed that standard predictive queries are frequently interpreted as requests to estimate the likelihood of E given C alone. In Experiment 2, a causal Bayes network overestimated predictive inference when it was queried in the standard way, but this overestimation diminished when predictive inference was queried using an alternative wording. In Experiment 3, participants judged alternative causes to be relevant to diagnostic inference and both disablers and alternative causes to be relevant to predictive inference. In Experiment 4, disablers greatly overshadowed alternative causes in predictive judgments, but their impact on diagnostic judgments was negligible. In Experiment 5, the order of disabler retrieval influenced causal judgments. Taken together, these results indicate that human causal inference cannot be adequately modeled unless the manner in which knowledge is retrieved and applied is taken into consideration., (PsycINFO Database Record (c) 2014 APA, all rights reserved.)

In their discussion of young children's deontic reasoning performance, Astington and Dack (2013) made the following claims: (1) Children need more cues to elicit cogent social norm reasoning than adults require, namely, explicit reference to authority; (2) Deontic reasoning improves with age, and this is evidence against a nativist view; (3) All evolutionary explanations of deontic reasoning advantages require positing a ''domain-specific deontic reasoning module."; and (4) young children excel at deontic reasoning because it is easier. Here, I refute each claim. Instead, I argue that (1) Social norm reasoning is one type of deontic reasoning that has been the target of selective pressure; (2) Development does not preclude nativism; (3) Epistemic utterances make no greater processing demands than deontic utterances; and (4) both adult and child norm reasoning performance is strongly influenced by reference to or implication of authority., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Dack and Astington (Journal of Experimental Child Psychology 110 2011 94-114) attempted to replicate the deontic reasoning advantage among preschoolers reported by Cummins (Memory & Cognition 24 1996 823-829) and by Harris and Nuñez (Child Development. 67 1996 572-1591). Dack and Astington argued that the apparent deontic advantage reported by these studies was in fact an artifact due to a methodological confound, namely, inclusion of an authority in the deontic condition only. Removing this confound attenuated the effect in young children but had no effect on the reasoning of 7-year-olds and adults. Thus, removing reference to authority "explains away" young children's apparent precocity at this type of reasoning. But this explanation rests on (a) a misunderstanding of norms as targets of deontic reasoning and (b) conclusions based on a sample size that was too small to detect the effect in young children., (Copyright © 2013 Elsevier Inc. All rights reserved.)

A cornerstone of economic theory is that rational agents are self-interested, yet a decade of research in experimental economics has shown that economic decisions are frequently driven by concerns for fairness, equity, and reciprocity. One aspect of other-regarding behavior that has garnered attention is noblesse oblige, a social norm that obligates those of higher status to be generous in their dealings with those of lower status. The results of a cross-cultural study are reported in which marked noblesse oblige was observed on a reciprocal-contract decision-making task. Participants from seven countries that vary along hierarchical and individualist/collectivist social dimensions were more tolerant of non-reciprocation when they adopted a high-ranking perspective compared with a low-ranking perspective.

According to an influential dual-process model, a moral judgment is the outcome of a rapid, affect-laden process and a slower, deliberative process. If these outputs conflict, decision time is increased in order to resolve the conflict. Violations of deontological principles proscribing the use of personal force to inflict intentional harm are presumed to elicit negative affect which biases judgments early in the decision-making process. This model was tested in three experiments. Moral dilemmas were classified using (a) decision time and consensus as measures of system conflict and (b) the aforementioned deontological criteria. In Experiment 1, decision time was either unlimited or reduced. The dilemmas asked whether it was appropriate to take a morally questionable action to produce a "greater good" outcome. Limiting decision time reduced the proportion of utilitarian ("yes") decisions, but contrary to the model's predictions, (a) vignettes that involved more deontological violations logged faster decision times, and (b) violation of deontological principles was not predictive of decisional conflict profiles. Experiment 2 ruled out the possibility that time pressure simply makes people more like to say "no." Participants made a first decision under time constraints and a second decision under no time constraints. One group was asked whether it was appropriate to take the morally questionable action while a second group was asked whether it was appropriate to refuse to take the action. The results replicated that of Experiment 1 regardless of whether "yes" or "no" constituted a utilitarian decision. In Experiment 3, participants rated the pleasantness of positive visual stimuli prior to making a decision. Contrary to the model's predictions, the number of deontological decisions increased in the positive affect rating group compared to a group that engaged in a cognitive task or a control group that engaged in neither task. These results are consistent with the view that early moral judgments are influenced by affect. But they are inconsistent with the view that (a) violation of deontological principles are predictive of differences in early, affect-based judgment or that (b) engaging in tasks that are inconsistent with the negative emotional responses elicited by such violations diminishes their impact.

Fairley and Manktelow (1997) have mistaken an error of presentation for an error of substance. My causal theory remains the same: Causal reasoning scenarios that require the reasoner to decide whether or not an effect will occur in the presence of a viable cause trigger consideration of disabling conditions&#x2014;that is, factors that could prevent the effect from occurring in the presence of a viable cause. Scenarios that require the reasoner to decide whether or not a particular cause has produced an observed effect trigger consideration of possible alternative causes. The data reported by Cummins (1995) and Cummins, Lubart, Alksnis, and Rist (1991) are consistent with this theoretical analysis.

Deontic reasoning is reasoning about what one may, ought, or ought not do in a given set of circumstances. Virtually all of our social institutions and child-rearing practices presume the capacity to reason about deontic concepts, such as what is permitted, obligated, or prohibited. Despite this, very little is known about the development of deontic reasoning. Two experiments were conducted that contrasted children's reasoning performance on deontic and indicative reasoning tasks (i.e., the reduced array selection version of the Wason card selection task). Like adults, children as young as 3 years of age were found to adopt a violation-detecting strategy more often when reasoning about the deontic case than when reasoning about the indicative case. These results indicate that violation detection emerges as an effective deontic reasoning very early in human development.

Evidence is presented that implicates two factors in deductive reasoning about causality. The factors are alternative causes and disabling conditions (factors that prevent effects from occurring in the presence of viable causes). A causal analysis is presented in which these factors impact on judgments concerning causal necessity and sufficiency, which in turn determine deductive entailment relations. In Experiment 1, these factors were found to impact causal deductive judgments more strongly than did logical form. In Experiment 2, causal deductive judgments were found to vary as a function of familiarity with a particular causal relationship: The more familiar the causal relationship, the less willing reasoners were to accept conclusions based on them.

An experiment was conducted to investigate the relative contributions of syntactic form and content to conditional reasoning. The content domain chosen was that of causation. Conditional statements that described causal relationships (if mean value of cause, then mean value of effect) were embedded in simple arguments whose entailments are governed by the rules of truth-functional logic (i.e., modus ponens, modus tollens, denying the antecedent, and affirming the consequent). The causal statements differed in terms of the number of alternative causes and disabling conditions that characterized the causal relationship. (A disabling condition is an event that prevents an effect from occurring even though a relevant cause is present). Subjects were required to judge whether or not each argument's conclusion could be accepted. Judgements were found to vary systematically with the number of alternative causes and disabling conditions. Conclusions of arguments based on conditionals with few alternative causes or disabling conditions were found to be more acceptable than conclusions based on those with many.