Citations

We describe the design and results from the BraTS 2023 Intracranial Meningioma Segmentation Challenge. The BraTS Meningioma Challenge differed from prior BraTS Glioma challenges in that it focused on meningiomas, which are typically benign extra-axial tumors with diverse radiologic and anatomical presentation and a propensity for multiplicity. Nine participating teams each developed deep-learning automated segmentation models using image data from the largest multi-institutional systematically expert annotated multilabel multi-sequence meningioma MRI dataset to date, which included 1000 training set cases, 141 validation set cases, and 283 hidden test set cases. Each case included T2, FLAIR, T1, and T1Gd brain MRI sequences with associated tumor compartment labels delineating enhancing tumor, non-enhancing tumor, and surrounding non-enhancing FLAIR hyperintensity. Participant automated segmentation models were evaluated and ranked based on a scoring system evaluating lesion-wise metrics including dice similarity coefficient (DSC) and 95% Hausdorff Distance. The top ranked team had a lesion-wise median dice similarity coefficient (DSC) of 0.976, 0.976, and 0.964 for enhancing tumor, tumor core, and whole tumor, respectively and a corresponding average DSC of 0.899, 0.904, and 0.871, respectively. These results serve as state-of-the-art benchmarks for future pre-operative meningioma automated segmentation algorithms. Additionally, we found that 1286 of 1424 cases (90.3%) had at least 1 compartment voxel abutting the edge of the skull-stripped image edge, which requires further investigation into optimal pre-processing face anonymization steps.

OBJECTIVE Cervical spondylotic myelopathy (CSM) can be associated with urinary dysfunction, leading to an inability or marked difficulty with micturition. This study aimed to evaluate the urinary dysfunction, long-term prognosis, and recovery in patients with CSM following surgical intervention. METHODS The CSM cases of the Quality Outcomes Database SpineCORe study group were analyzed. Urinary control was assessed using the modified Japanese Orthopaedic Association (mJOA) urinary function subscore. Improvement was defined as a minimum improvement of 1 point in the mJOA urinary function subscore at the 2-year follow-up. Univariate and multivariable analyses were conducted as appropriate. RESULTS Of 1141 patients, 772 (67.7%) patients were identified with a minimum 2-year follow-up mJOA score, and 249 (32.3%) of these patients reported baseline urinary dysfunction. Of those 249 patients with baseline urinary control problems, 193 (77.5%) had improvement in urinary function postoperatively, and more women than men had improved urinary control after CSM surgery (54.9% vs 45.1%, p = 0.03). Apart from sex, demographic characteristics of patients who experienced urinary function improvement versus those who did not were similar. Patients who experienced urinary function improvement had lower overall baseline mJOA scores (10.2 vs 13, p < 0.01). Both cohorts reported similar rates of postoperative satisfaction (North American Spine Society scores of 1 and 2) (89.1% vs 85.9%, p = 0.26). CONCLUSIONS Among the one-third of patients with CSM experiencing urinary dysfunction, nearly 78% achieve improved urinary function at the 2-year postoperative follow-up. Women are more likely to experience improvement in this function. Patients with and without improvements in urinary function are equally satisfied with their surgery and report similar outcomes on long-term follow-up.

Abstract INTRODUCTION Early‐onset and late‐onset Alzheimer's disease (EOAD and LOAD, respectively) have distinct clinical manifestations, with prior work based on small samples suggesting unique patterns of neurodegeneration. The current study performed a head‐to‐head comparison of cortical atrophy in EOAD and LOAD, using two large and well‐characterized cohorts (LEADS and ADNI). METHODS We analyzed brain structural magnetic resonance imaging (MRI) data acquired from 377 sporadic EOAD patients and 317 sporadicLOAD patients who were amyloid positive and had mild cognitive impairment (MCI) or mild dementia (i.e., early‐stage AD), along with cognitively unimpaired participants. RESULTS After controlling for the level of cognitive impairment, we found a double dissociation between AD clinical phenotype and localization/magnitude of atrophy, characterized by predominant neocortical involvement in EOAD and more focal anterior medial temporal involvement in LOAD. DISCUSSION Our findings point to the clinical utility of MRI‐based biomarkers of atrophy in differentiating between EOAD and LOAD, which may be useful for diagnosis, prognostication, and treatment. Highlights Early‐onset Alzheimer's disease (EOAD) and late‐onset AD (LOAD) patients showed distinct and overlapping cortical atrophy patterns. EOAD patients showed prominent atrophy in widespread neocortical regions. LOAD patients showed prominent atrophy in the anterior medial temporal lobe. Regional atrophy was correlated with the severity of global cognitive impairment. Results were comparable when the sample was stratified for mild cognitive impairment (MCI) and dementia.

OBJECTIVE It is not clear whether smoking impacts patient-reported outcomes (PROs) in patients with cervical spondylotic myelopathy (CSM). The aim of this study was to explore the impact of smoking status on baseline symptom severity and the rate of achieving satisfaction and the minimal clinically important differences (MCIDs) for PROs in patients with CSM. METHODS This study was an analysis of the prospective Quality Outcomes Database CSM module. Patients aged ≥ 18 years diagnosed with primary CSM who underwent elective surgery were included. PROs (visual analog scale [VAS] neck and arm pain, Neck Disability Index [NDI], modified Japanese Orthopaedic Association [mJOA], and EQ-5D scores and North American Spine Society [NASS] patient satisfaction) were collected at baseline and 24 months of follow-up. RESULTS Of the 1141 patients with CSM, 202 (17.7%) were smokers and 939 (82.3%) were nonsmokers. Compared with the nonsmokers, smokers were younger (56.3 ± 11.3 years vs 61.5 ± 11.7 years, p < 0.01) and had a lower BMI (29.3 ± 6.8 vs 30.3 ± 6.3, p = 0.04). A higher proportion of smokers had depression, anxiety, and chronic obstructive pulmonary disease (all p < 0.01). At baseline, smokers had worse pain (VAS neck pain score: 6.0 ± 3.2 vs 5.1 ± 3.3; VAS arm pain score: 5.7 ± 3.2 vs 4.7 ± 3.5), disability (NDI score: 45.2 ± 20.0 vs 37.1 ± 20.6), myelopathy (mJOA score: 11.5 ± 2.9 vs 12.2 ± 2.8), and quality of life (EQ-5D score: 0.51 ± 0.23 vs 0.57 ± 0.22) (all p < 0.01). At the 24-month follow-up, a higher proportion of smokers achieved the MCID in mJOA (69.4% vs 56.6%, p < 0.01) compared with nonsmokers. However, after accounting for significant covariates, there was no significant difference in the baseline disease severity. There was also no difference between the PROs at the 24-month follow-up. The two groups also achieved similar MCIDs for most PROs and were similarly satisfied (NASS score of 1 or 2: smoker 81.2% vs nonsmoker 84.6%, p = 0.29) 24 months after surgery. CONCLUSIONS Smokers and nonsmokers with CSM had similar baseline disease severity and 24-month PROs. They also achieved similar rates of MCIDs for PROs and satisfaction after surgery. Numerous previous studies have documented the association between tobacco usage and inferior clinical outcomes after spine surgery. However, in the context of severe and debilitating spinal disorders such as cervical myelopathy, meaningful and impactful improvements are still seen in properly selected patients.

OBJECTIVE Cervical spondylotic myelopathy (CSM) shows varying levels of improvement after surgical treatment. While some patients improve soon after surgery, others may take months to years to show any signs of improvement. The goal of this study was to evaluate postoperative improvement, patient-reported outcomes, and patient satisfaction up to 2 years after surgical treatment for CSM, which will help optimize the current treatment strategies and effectively manage patient expectations. METHODS This was a retrospective study of prospectively collected data using the Quality Outcomes Database. The primary outcomes of interest were achievement of the minimal clinically important difference (MCID) for the numeric rating scale for neck and arm pain, modified Japanese Orthopaedic Association, Neck Disability Index, and EQ-5D scores and postoperative satisfaction (North American Spine Society scale). Early and sustained improvement was defined as MCID achievement in at least one patient-reported outcome measure (PROM) at the 3-, 12-, and 24-month follow-ups. Transient improvement was defined as MCID achievement only at the 3-month and/or 12-month follow-up but not at the 24-month follow-up. Late improvement was defined as MCID achievement in at least one PROM only at the 24-month follow-up. RESULTS There were 630 patients included in the comparative analysis. A total of 463 (73.5%) patients achieved early and sustained improvement, 105 (16.7%) patients experienced transient improvement with subsequent decline, 25 (4.0%) patients reported late improvement, and 37 (5.9%) patients did not report any clinically meaningful improvement after surgery. Patients with an anterior approach were more likely to be in the early and sustained improvement group. African American patients (OR 2.98, 95% CI 1.14–7.76; p = 0.03) were more likely to report late improvement when compared with White patients. The overall satisfaction rate at the 24-month follow-up was 87.8%. CONCLUSIONS These findings indicate that 73.5% of patients achieve early and sustained improvement, and 87.8% of patients are satisfied with surgery 24 months postoperatively.

Abstract INTRODUCTION Early‐onset Alzheimer's disease (EOAD) manifests prior to the age of 65, and affects 4%–8% of patients with Alzheimer's disease (AD). The current analyses sought to examine longitudinal cognitive trajectories of participants with early‐onset dementia. METHODS Data from 307 cognitively normal (CN) volunteer participants and those with amyloid‐positive EOAD or amyloid‐negative cognitive impairment (EOnonAD) were compared. Cognitive trajectories across a comprehensive cognitive battery spanning 42 months were examined using mixed‐effects modeling. RESULTS The EOAD group displayed worse cognition at baseline relative to EOnonAD and CN groups, and more aggressive declines in cognition over time. The largest effects were observed on measures of executive functioning domains, while memory declines were blunted in EOAD. DISCUSSION EOAD declined 2–4× faster than EOnonAD, and EOAD pathology is not restricted to memory networks. Early identification of deficits is critical to ensure that individuals with sporadic EOAD can be considered for treatment using disease‐modifying medications. Highlights Represents the most comprehensive longitudinal characterization of sporadic EOAD to date. The trajectory of cognitive declines was steep for EOAD participants and worse than for other groups. Executive functioning measures exhibited the greatest declines over time in EOAD.

Abstract INTRODUCTION Early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) share similar amyloid etiology, but evidence from smaller‐scale studies suggests that they manifest differently clinically. Current analyses sought to contrast the cognitive profiles of EOAD and LOAD. METHODS Z‐ score cognitive‐domain composites for 311 amyloid‐positive sporadic EOAD and 314 amyloid‐positive LOAD participants were calculated from baseline data from age‐appropriate control cohorts. Z‐ score composites were compared between AD groups for each domain. RESULTS After controlling for cognitive status, EOAD displayed worse visuospatial, executive functioning, and processing speed/attention skills relative to LOAD, and LOAD displayed worse language, episodic immediate memory, and episodic delayed memory. DISCUSSION Sporadic EOAD possesses distinct cognitive profiles relative to LOAD. Clinicians should be alert for non‐amnestic impairments in younger patients to ensure proper identification and intervention using disease‐modifying treatments. Highlights Both early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) participants displayed widespread cognitive impairments relative to their same‐aged peers. Cognitive impairments were more severe for EOAD than for LOAD participants in visuospatial and executive domains. Memory and language impairments were more severe for LOAD than for EOAD participants Results were comparable after removing clinical phenotypes of posterior cortical atrophy (PCA), primary progressive aphasia (lv‐PPA), and frontal‐variant AD.

ObjectiveVagus nerve stimulation (VNS) paired with rehabilitation therapy improved motor status compared to rehabilitation alone in the phase III VNS‐REHAB stroke trial, but treatment response was variable and not associated with any clinical measures acquired at baseline, such as age or side of paresis. We hypothesized that neuroimaging measures would be associated with treatment‐related gains, examining performance of regional injury measures versus global brain health measures in parallel with clinical measures.MethodsBaseline magnetic resonance imaging (MRI) scans in the VNS‐REHAB trial were used to derive regional injury measures (extent of injury to corticospinal tract, the primary regional measure; plus extent of injury to precentral gyrus and postcentral gyrus; lesion volume; and lesion topography) and global brain health measures (degree of white matter hyperintensities, the primary global brain measure; plus volumes of cerebrospinal fluid, cortical gray matter, white matter, each thalamus, and total brain). Eight clinical measures assessed at baseline were also evaluated (treatment group, age, race, gender, paretic side, pre‐stroke dominant hand, time since stroke, and baseline Fugl‐Meyer upper extremity score). Bivariate analyses compared each measure with the primary trial end point (change in Fugl‐Meyer upper extremity score from baseline to end of 6 weeks of treatment) across all subjects, with secondary analyses examining trial groups separately.ResultsMRIs were available from 80 patients (age = 59.8 ± 9.5 years, 29 women). Across all patients, less white matter hyperintensities (r = −0.25, p = 0.028) at baseline was associated with larger Fugl‐Meyer score change. In the VNS group, less white matter hyperintensities (r = −0.37, p = 0.018) and larger ipsilesional thalamus volume (r = 0.33, p = 0.046) were each associated with larger Fugl‐Meyer score change. Analysis of covariance (ANCOVA) analyses tested the interaction that each baseline measure had with treatment group and found that the model examining white matter hyperintensities had a significant interaction term, indicating 2.3 less change in Fugl‐Meyer Upper Extremity (FM‐UE) points in the VNS group relative to the control group for each point increase in modified Fazekas scale.InterpretationNeuroimaging measures are associated with extent of gains on the primary endpoint of a phase III stroke recovery trial. Among the neuroimaging measures examined, a measure of global brain health (extent of white matter hyperintensities) was better at explaining the change in arm impairment as compared with measures of regional injury; this was true when examining all study subjects as well as only those in the VNS group and is consistent with the global mechanism of action that VNS has throughout the cerebrum. Future studies can evaluate additional measures that further predict response to VNS therapy. The current findings suggest that individual patient neuroimaging results may be useful for a personalized medicine approach to stroke recovery therapeutics. ANN NEUROL 2025;97:709–719

Importance Neoadjuvant therapy (NT) is an increasingly used treatment strategy for patients with localized pancreatic ductal adenocarcinoma (PDAC). Little research has been conducted on cancer care delivery during NT, and the standards for optimal delivery of NT have not been defined. Objective To develop consensus best practices for delivering NT to patients with localized PDAC. Design, Setting, and Participants This study used a modified Delphi approach consisting of 2 rounds of voting, and a series of virtual conferences (from October to December 2023) to reach expert consensus on candidate best practice statements generated from a systematic review of the literature and expert opinion. An interdisciplinary panel was formed including 47 North American experts from surgical, medical, and radiation oncology, radiology, pathology, gastroenterology, integrative oncology, anesthesia, pharmacy, nursing, cancer care delivery research, and nutrition as well as patient and caregiver stakeholders. Main Outcome and Measures Statements that reached 75% agreement or greater were included in final consensus statements. Results Of the 47 participating panel members, 27 (57.64%) were male, and the mean (SD) age was 47.6 (8.2) years. Physicians reported completing training a mean (SD) 14.6 (8.6) years prior and seeing a mean (SD) 110.6 (38.4) patients with PDAC annually; 35 (77.7%) were in academic practice. Final consensus was reached on 82 best practices for delivering NT. Of these, 38 statements focused on pre-NT practices, including diagnosis and staging (n = 15), evaluation and optimization (n = 20), and decision-making (n = 3); 29 statements defined best practices during NT, including initiation (n = 3), delivery of therapy (n = 8), restaging practices (n = 12), and management of complications during NT (n = 6); and 15 best practices were identified to guide treatment post-NT, focusing on surgery (n = 7), pathology (n = 4), and follow-up (n = 3). Conclusions Using a modified Delphi consensus technique, best practice guidelines were developed focusing on the optimal standards for delivering NT to patients with localized PDAC. Given the prognostic importance of completing multimodality therapy, efforts to standardize and optimize the delivery of NT represent an immediate opportunity to decrease care variation and improve outcomes for patients with PDAC. Future research should focus on validating and implementing best practice standards into clinical practice.