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Most people who develop dementia will never be diagnosed, and therefore lack access to treatment and care from specialists in the field. This new edition provides updated guidance on how behavioral symptom reflect the changes occurring in the brain, and how these can help generalist clinicians to accurately diagnose neurodegenerative diseases. This practical book is aimed at healthcare professionals working in neurology, psychiatry and neuropsychology wanting to enhance the skills and knowledge needed to successfully manage these diseases. Simple approaches to bedside mental status testing, differential diagnosis and treatment, and interpreting neuropsychological testing and neuroimaging findings are covered. Introductory chapters outline dementia epidemiology and dementia neuropathology whilst chapters new to this edition describe the improvements in diagnostic capabilities in recent years, including blood based and cerebrospinal biomarkers and emerging biologically based therapies. Chapters on sleep disorders, and chronic traumatic encephalopathy and traumatic brain injury have also been expanded.
Graduates from life sciences, including nutrition, will be at the forefront of promoting environmental, social, and food systems sustainability. The requisite competencies for their future roles include systems thinking, interdisciplinary collaboration, and effective communication, which are essential to navigating the complex interrelationship between human health and the environment [1,2]. To address this need, a 'Living Laboratory’ (LL) within a higher education (HE) food service setting could enrich the traditional laboratory experience, allowing students to cultivate these skills through experiential learning. This project aimed to i) scope the published literature to characterise LL examples within a HE food environment and ii) explore the understanding and perceptions of a LL concept in a food service setting for final year student research projects among students and academics at King’s College London.
A systematic scoping review was conducted in accordance with PRISMA-ScR guidelines (Registration OSF:d7y96). Two databases were searched (PubMed/Medline, Web of Science) from January 2010 to July 2024 to identify articles reporting the design, implementation or evaluation of LL in HE food service settings. A narrative synthesis was performed, and the resulting themes were used to inform focus groups (KCL Ethics:LRM-23/24-42657) with academic staff (two groups, nine participants) and students (four groups, seven postgraduate and nine undergraduate participants). Focus group discussions were audio-recorded and transcribed verbatim. Data were analysed using an inductive thematic approach [3].
Twenty-one articles were included in the scoping review. Common terms used to describe the LL concept included ‘innovation’, ‘collaboration’, ‘diverse stakeholders’, ‘enabling students’ and ‘practical learning experiences’. Recommendations for implementing LLs were provided in six articles and included engagement and outreach with stakeholders; managing conflicts; assessing impact; and establishing ethical and governance frameworks. The focus group findings indicated that both students and academics view the LL concept as a dynamic, real-world setting, emphasizing engagement and collaboration with internal and external stakeholders. Academics perceived the educational benefits of LLs as fostering experiential learning and perceived the barriers to implementation as including a lack of resources, scheduling conflicts, insufficient stakeholder engagement and unclear governance frameworks. Students highlighted the importance of aligning projects with taught programme content. and identified challenges such as limited awareness, unequal engagement across disciplines, time constraints, and concerns about inclusivity and equity across campuses. Students agreed that the LL provided opportunities to develop skills and knowledge in sustainability, science communication and real-world evidence studies, opening new career options after graduation. Lastly, altruism to improve food environments for peers and future students was a significant driving factor in student engagement.
Implementing LLs in HE food service settings requires input from multiple stakeholders. This scoping project identified key considerations from both academic staff and students to inform the co-design of a LL in a HE food service setting.
Visceral larva migrans syndrome (VLM) is caused by L2 Toxocara canis. This parasitic disease is difficult to diagnose in humans, but specific antigen identification could allow for parasite detection. The aim of this study was to analyse antigens of different parasite developmental stages and observe their cross-reactions with antigens from other parasites to determine their importance in the diagnosis of VLM caused by T. canis. Sera from 14 children with cryptogenic epilepsy previously positive for T. canis were analysed via Western blot (WB) using T. canis excretion-secretion antigens (TESs) from distinct morphological parasite stages; cross-reactivity of these antigens with antigens from other parasites were evaluated. Children sera recognized antigens from L2 T. canis TES, mainly a protein of 24 kDa. Proteins in the medium- and high-molecular-weight ranges were also detected in the egg phase. In the adult phase, only 42.9% of analysed sera recognized a protein of high-molecular weight. Cross-reaction tests identified medium and high-molecular weight proteins, mainly from L2 of Ascaris lumbricoides and Gnathostoma binucleatum and adults of Ancylostoma caninum, but none of the proteins found had crossover with low-molecular weight proteins from Toxocara canis. Antigens in the larval morphological stage of T. canis TES were recognized in the highest percentage of the analysed sera; these antigens could be used to diagnose VLM.
Impairments in social interaction are common symptoms of dementia and necessitate the use of validated neuropsychological instruments to measure social cognition. We aim to investigate the Hinting Task – Dutch version (HT-NL), which measures the ability to infer intentions behind indirect speech to assess Theory of Mind, in dementia.
Method:
Sixty-six patients with dementia, of whom 22 had behavioral variant frontotemporal dementia (bvFTD), 21 had primary progressive aphasia, and 23 had Alzheimer’s disease (AD), and 99 healthy control participants were included. We examined the HT-NL’s psychometric properties, including internal consistency, between-group differences using analyses of covariance with Bonferroni-adjusted post hoc comparisons, discriminative ability and concurrent validity using the area under the receiver operating characteristic curve (AUC), and construct validity using Spearman rank correlations with other cognitive tests.
Results:
Internal consistency was acceptable (Cronbach’s α = 0.74). All patient groups scored lower on the HT-NL than the control group. Patients with bvFTD scored lower than patients with AD dementia. The HT-NL showed excellent discriminative ability (AUC = 0.83), comparable to a test of emotion recognition (ΔAUC = 0.03, p = .67). The HT-NL correlated significantly with a test for emotion recognition (r = .45), and with measures of memory and language (r = [.31, .40]), but not with measures of information processing speed, executive functioning, or working memory (r = [.00, .17]). Preliminary normative data are provided.
Conclusions:
The HT-NL is a psychometrically sound and valid instrument and is useful for identifying Theory of Mind impairments in patients with dementia.
Progressive ventricular remodelling in children with repaired tetralogy of Fallot may or may not result in the need for pulmonary valve replacement. We aimed to model and compare the rates of right and left ventricular adaptation over time, as assessed by cardiac MRI after surgical repair of tetralogy of Fallot, in children who did or did not require pulmonary valve replacement later in adolescence.
Methods:
Single-centre, retrospective cohort study from 2000 to 2020 including patients with tetralogy of Fallot who had complete surgical repair before 24 months.
Results:
From 214 patients included in this analysis, 142 (66.3%) had pulmonary valve replacement at a median age of 12 years (interquartile range 9–15.5) during follow-up. Assessing 323 cardiac MRI studies from 201 patients commencing from a median age of 9.4 years (interquartile range 5.9–12.3), the group that required pulmonary valve replacement later during the follow-up had a steeper time-related right ventricular dilation trajectory than non-pulmonary valve replacement patients: the increment in right ventricular end-diastolic volume index was 19.4 versus 2.8 ml/m2/log2year, P < 0.001; also, right ventricular end-systolic volume index incremented more quickly, at 11.9 versus 0.8 ml/m2/log2year, P < 0.001. Left ventricular end-diastolic volume index increased more quickly in patients who eventually had pulmonary valve replacement, at 7.2 versus 1.5 ml/m2/log2year, P = 0.005; the same occurred for indexed left ventricular end-systolic volume at 3.2 versus –0.4 ml/m2/log2year, P = 0.001.
Conclusion:
Early right and left ventricular dilation over time are identifiable by cardiac MRI in patients destined to require pulmonary valve replacement following tetralogy of Fallot repair.
The estimated global preterm birth rate in 2020(1) was more than 10% of livebirths or 13.4 million infants. Despite the importance of neonatal nutrition in optimising growth, neurodevelopment, and later metabolic disease risk, there is inconsistency in nutrition recommendations for preterm infants(2). Incomplete or inconsistent reporting of outcomes in nutrition intervention studies is part of the reason for the lack of consensus on optimal nutrition. To reduce uncertainty in measuring or reporting nutritional intake and growth outcomes in preterm studies, a consensus process is needed to identify relevant measures for patients, parents/caregivers, researchers, and health professionals. We aimed to develop a minimum reporting set (MRS) for measures of nutritional intake and growth in preterm nutrition studies. We collaborated with a group of international researchers from 13 countries and registered this study at the COMET initiative (registration number 3185). The target population was individuals born preterm at any gestational age and study location whose nutritional intake was assessed before first hospital discharge and whose growth was assessed at any age. Measures reported in preterm nutrition studies were systematically reviewed and used to develop the real-time Delphi survey(3) using Surveylet (Calibrum) software, including 13 questions about nutritional intake and 14 about growth outcomes. We used a snowball process to recruit participants from the consumer, healthcare provider, and researcher stakeholder groups with expertise in preterm infants, nutrition, and growth to rate the importance of each measure on a 9-point Likert scale. Participants initially rated the survey items without seeing other participants’ responses, saved and refreshed the page to see the anonymous responses of other participants, and had the option to change their rating and provide reasons for their answers. Participants’ final scores for each item will be used to identify the consensus criteria for that item(3). To date, we have recruited 246 participants from 31 countries across 5 continents, including 58 (24%) consumers, 156 (63%) healthcare professionals, and 26 (11%) researchers. Preliminary findings indicate that 12 measures of nutritional intake and 4 of growth have met the criteria for inclusion in the MRS. However, participant recruitment and survey responses are ongoing. A final consensus meeting is planned for November 2024 to confirm the MRS.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Most cognitive studies of bipolar disorder (BD) have examined case–control differences on cognitive tests using measures of central tendency, which do not consider intraindividual variability (IIV); a distinct cognitive construct that reliably indexes meaningful cognitive differences between individuals. In this study, we sought to characterize IIV in BD by examining whether it differs from healthy controls (HCs) and is associated with other cognitive measures, clinical variables, and white matter microstructure.
Methods
Two hundred and seventeen adults, including 100 BD outpatients and 117 HCs, completed processing speed, sustained attention, working memory, and executive function tasks. A subsample of 55 BD participants underwent diffusion tensor imaging. IIV was operationalized as the individual standard deviation in reaction time on the Continuous Performance Test-Identical Pairs version.
Results
BD participants had significantly increased IIV compared to age-matched controls. Increased IIV was associated with poorer mean performance scores on processing speed, sustained attention, working memory, and executive function tasks, as well as two whole-brain white matter indices: fractional anisotropy and radial diffusivity.
Conclusions
IIV is increased in BD and appears to correlate with other cognitive variables, as well as white matter measures that index reduced structural integrity and demyelination. Thus, IIV may represent a neurobiologically informative cognitive measure for BD research that is worthy of further investigation.
Indaziflam (Rejuvra®), a preemergence herbicide first registered in vine and tree nut crops, was recently approved for applications to rangeland for winter annual grass control. Indaziflam controls cheatgrass (Bromus tectorum L.) for at least 3 yr, and control can extend into a fourth and fifth year; however, it is very difficult to find indaziflam residues in the soil 2 yr after application. Indaziflam could be absorbed by seeds still retained on the plant and on the soil surface in sufficient concentrations to stop establishment. To test this hypothesis, B. tectorum seeds and jointed goatgrass (Aegilops cylindrica Host) spikelets were treated with indaziflam and imazapic at rates from 5.4 to 175 g ai ha−1 using a greenhouse track sprayer delivering 187 L ha−1. Treated seeds were planted into field soil, and plants were allowed to grow for 21 d under greenhouse conditions. Growth was compared with growth of non-treated controls. In addition, a second set of treated seeds were exposed to rainfall 1 and 24 h after treatment and rainfall amounts ranging from 3 to 24 mm to determine whether rainfall impacted herbicide performance. Bromus tectorum was so sensitive to indaziflam that establishment was eliminated at all rates. Imazapic inhibited B. tectorum establishment with an ED90 of 67 g ai ha−1. Indaziflam effectively inhibits A. cylindrica establishment with an ED90 of 7.4 g ai ha−1 compared with imazapic with an ED50 of 175 g ai ha−1. Indaziflam’s impact on A. cylindrica establishment was not significantly impacted by rainfall, indicating that the herbicide was absorbed to the seed coat. These findings support the hypothesis that indaziflam’s long-term control could result from its ability to inhibit establishment of seeds retained in the canopy and those on the soil surface at the time of application.
This is a proof-of-concept study to compare the effects of a 2-week program of “Remind-to-move” (RTM) treatment using closed-loop and open-loop wearables for hemiparetic upper extremity in patients with chronic stroke in the community. The RTM open-loop wearable device has been proven in our previous studies to be useful to address the learned nonuse phenomenon of the hemiparetic upper extremity. A closed-loop RTM wearable device, which emits reminding cues according to actual arm use, was developed in this study. A convenience sample of 16 participants with chronic unilateral stroke recruited in the community was engaged in repetitive upper extremity task-specific practice for 2 weeks while wearing either a closed-loop or an open-loop ambulatory RTM wearable device on their affected hand for 3 hrs a day. Evaluations were conducted at pre-/post-intervention and follow-up after 4 weeks using upper extremity motor performance behavioral measures, actual arm use questionnaire, and the kinematic data obtained from the device. Results showed that both open-loop and closed-loop training groups achieved significant gains in all measures at posttest and follow-up evaluations. The closed-loop group showed a more significant improvement in movement frequency, hand functions, and actual arm use than did the open-loop group. Our findings supported the use of closed-loop wearables, which showed greater effects in terms of promoting the hand use of the hemiparetic upper extremity than open-loop wearables among patients with chronic stroke.
Characterizing the structure and composition of clay minerals on the surface of Mars is important for reconstructing past aqueous processes and environments. Data from the CheMin X-ray diffraction (XRD) instrument on the Mars Science Laboratory Curiosity rover demonstrate a ubiquitous presence of collapsed smectite (basal spacing of 10 Å) in ~3.6-billion-year-old lacustrine mudstone in Gale crater, except for expanded smectite (basal spacing of 13.5 Å) at the base of the stratigraphic section in a location called Yellowknife Bay. Hypotheses to explain expanded smectite include partial chloritization by Mg(OH)2 or solvation-shell H2O molecules associated with interlayer Mg2+. The objective of this work is to test these hypotheses by measuring partially chloritized and Mg-saturated smectite using laboratory instruments that are analogous to those on Mars rovers and orbiters. This work presents Mars-analog XRD, evolved gas analysis (EGA), and visible/shortwave-infrared (VSWIR) data from three smectite standards that were Mg-saturated and partially and fully chloritized with Mg(OH)2. Laboratory data are compared with XRD and EGA data collected from Yellowknife Bay by the Curiosity rover to examine whether the expanded smectite can be explained by partial chloritization and what this implies about the diagenetic history of Gale crater. Spectral signatures of partial chloritization by hydroxy-Mg are investigated that may allow the identification of partially chloritized smectite in Martian VSWIR reflectance spectra collected from orbit or in situ by the SuperCam instrument suite on the Mars 2020 Perseverance rover. Laboratory XRD and EGA data of partially chloritized saponite are consistent with data collected from Curiosity. The presence of partially chloritized (with Mg(OH)2) saponite in Gale crater suggests brief interactions between diagenetic alkaline Mg2+-bearing fluids and some of the mudstone exposed at Yellowknife Bay, but not in other parts of the stratigraphic section. The location of Yellowknife Bay at the base of the stratigraphic section may explain the presence of alkaline Mg2+-bearing fluids here but not in other areas of Gale crater investigated by Curiosity. Early diagenetic fluids may have had a sufficiently long residence time in a closed system to equilibrate with basaltic minerals, creating an elevated pH, whereas diagenetic environments higher in the section may have been in an open system, therefore preventing fluid pH from becoming alkaline.
A Rank Forum was convened to discuss the evidence around food insecurity (FIS), its impact on health, and interventions which could make a difference both at individual and societal level, with a focus on the UK. This paper summarises the proceedings and recommendations. Speakers highlighted the growing issue of FIS due to current economic and social pressures. It was clear that the health implications of FIS varied geographically since food insecure women in higher income regions tend to be living with overweight or obesity, in contrast to those living in low-to-middle income countries. This paradox could be due to stress and/or metabolic or behavioural responses to an unpredictable food supply. The gut microbiota may play a role given the negative effects of low fibre diets on bacterial diversity, species balance and chronic disease risk. Solutions to FIS involve individual behavioural change, targeted services and societal/policy change. Obesity-related services are currently difficult to access. Whilst poverty is the root cause of FIS, it cannot be solved simply by making healthy food cheaper due to various ingrained beliefs, attitudes and behaviours in target groups. Person-centred models, such as Capability-Opportunity-Motivation Behavioural Change Techniques and Elicit-Provide-Elicit communication techniques are recommended. Societal change or improved resilience through psychological support may be more equitable ways to address FIS and can combine fiscal or food environment policies to shift purchasing towards healthier foods. However, policy implementation can be slow to enact due to the need for strong evidence, consultation and political will. Eradicating FIS must involve co-creation of interventions and policies to ensure that all stakeholders reach a consensus on solutions.
Background: The complement C5 inhibitor (C5IT), ravulizumab, is approved in Canada for the treatment of anti-acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG). Updated effectiveness and safety results from the ongoing MG SPOTLIGHT Registry (NCT04202341) are reported. Methods: MGFA classification and MG-ADL total scores were assessed in patients who received ravulizumab only (ravu-only) or transitioned from eculizumab to ravulizumab (ecu-to-ravu), with data available prior to C5IT initiation (“pre-C5IT”) and ≥1 assessment post-initiation (“post-ravu”). Results: Of 52 patients with 2 post-ravu assessments, average treatment duration was 10.4 months at last assessment (LA). Mean±SD MG-ADL scores improved (pre-C5IT: 7.6±3.6; LA: 3.4±3.3), as did the proportions of patients with minimal symptom expression (MSE, MG-ADL≤1) (pre-C5IT: 1/52 [2%]; LA: 17/52 [33%]) and MGFA classification 0-II (pre-C5IT: 18/45 [40%]; LA: 40/45 [89%]). In the ravu-only subgroup, outcomes improved (pre-C5IT vs LA): MG-ADL, 6.3±3.0 vs 4.0±3.4; MGFA 0-II, 9/14 [64%] vs 12/14 [86%]. The ecu-to-ravu subgroup sustained continued gradual improvement from last eculizumab assessment to LA: MG-ADL, 4.4±4.2 vs 3.0±2.8; MGFA 0-II, 19/21 [90%] vs 20/21 [95%]. Ravulizumab was well tolerated; no meningococcal infections were reported. Conclusions: These results demonstrate the long-term effectiveness and safety of ravulizumab in routine clinical practice in patients with gMG.
Background: Meningiomas are the most common intracranial tumors. Radiotherapy (RT) serves as an adjunct following surgical resection; however, response varies. RTOG-0539 is a prospective, phase 2, trial that stratified patients risk groups based on clinical and pathological criteria, providing key benchmarks for RT outcomes. This is the first study that aims to characterize the molecular landscape of an RT clinical trial in meningiomas. Methods: Tissue from 100 patients was analyzed using DNA methylation, RNA sequencing, and whole-exome sequencing. Copy number variations and mutational profiles were assessed to determine associations with meningioma aggressiveness. Tumors were molecularly classified and pathway analyses were conducted to identify biological processes associated with RT response. Results: High-risk meningiomas exhibited cell cycle dysregulation and hypermetabolic pathway upregulation. 1p loss and 1q gain were more frequent in aggressive meningiomas, and NF2 and non-NF2 mutations co-occurred in some high-risk tumors. Molecular findings led to the reclassification of several cases, highlighting the limitations of histopathologic grading alone. Conclusions: This is the first study to comprehensively characterize the molecular landscape of any RT trial in meningioma, integrating multi-omic data to refine treatment stratification. Findings align with ongoing genomically driven meningioma clinical trials and underscore the need for prospective tissue banking to enhance biomarker-driven treatment strategies.
Background: Polymicrobial brain abscess (PBA) is a complex infection caused by two or more pathogens and a life-threatening condition with diagnostic and therapeutic challenges. Methods: We retrospectively identified PBAs in 31 patients (a median of 58 years; 24 male, and 7 female) then examined their clinical, radiological and pathological characteristics. These characteristics of PBAs were compared with those of monomicrobial BAs (MBAs) in the previously reported 113 patients. Results: PBAs and MBAs had a few similarities such as nonspecific clinical presentations and overall similar prognosis following surgical intervention with broad-spectrum antimicrobial therapy. However, PBAs were highly heterogeneous with more complexity on MRI/CT imaging and histopathology. While PBAs were typically rim-enhancing lesions at late-stages, 30/31 (97%) of PBAs showed the lobulation of enhancing rims/walls; on MRI, 14/26 (54%) of cases demonstrated marked difference in the thickness of enhancing rim, marked difference in the degree of DWI signal, and/or marked variation in intra-lesional MRI signal. PBA histopathology was characterized by alternating early-stage and late-stage features with a combinations of 2-4 pathogens. Conclusions: BPAs share some features with MBAs, but they are more heterogeneous with greater complexity on imaging and histopathology. Their diagnosis and disease staging require a clinico-radiologico-pathological approach.
Background: The WHO grade of meningioma was updated in 2021 to include homozygous deletions of CDKN2A/B and TERT promotor mutations. Previous work including the recent cIMPACT-NOW statement have discussed the potential value of including chromosomal copy number alterations to help refine the current grading system. Methods: Chromosomal copy number profiles were inferred from from 1964 meningiomas using DNA methylation. Regularized Cox regresssion was used to identify CNAs independenly associated with post-surgical and post-RT PFS. Outcomes were stratified by WHO grade and novel CNAs to assess their potential value in WHO critiera. Results: Patients with WHO grade 1 tumours and chromosome 1p loss had similar outcomes to those with WHO grade 2 tumours (median PFS 5.83 [95% CI 4.36-Inf] vs 4.48 [4.09-5.18] years). Those with chromosome 1p loss and 1q gain had similar outcomes to those with WHO grade 3 cases regardless of initial grade (median PFS 2.23 [1.28-Inf] years WHO grade 1, 1.90 [1.23-2.25] years WHO grade 2, compared to 2.27 [1.68-3.05] years in WHO grade 3 cases overall). Conclusions: We advocate for chromosome 1p loss being added as a criterion for a CNS WHO grade of 2 meningioma and addition of 1q gain as a criterion for a CNS WHO grade of 3.
Background: We previously developed a DNA methylation-based risk predictor for meningioma, which has been used locally in a prospective fashion. As a follow-up, we validate this model using a large prospective cohort and introduce a streamlined next-generation model compatible with newer methylation arrays. Methods: The performance of our next-generation predictor was compared with our original model and standard-of-care 2021 WHO grade using time-dependent receiver operating characteristic curves. A nomogram was generated by incorporating our methylation predictor with WHO grade and extent of resection. Results: A total of 1347 meningioma cases were utilized in the study, including 469 prospective cases from 3 institutions and a retrospective cohort of 100 WHO grade 2 cases for model validation. Both the original and next-generation models significantly outperformed 2021 WHO grade in predicting postoperative recurrence. Dichotomizing into grade-specific risk subgroups was predictive of outcome within both WHO grades 1 and 2 tumours (log-rank p<0.05). Multivariable Cox regression demonstrated benefit of adjuvant radiotherapy in high-risk cases specifically, reinforcing its informative role in clinical decision making. Conclusions: This next-generation DNA methylation-based meningioma outcome predictor significantly outperforms 2021 WHO grading in predicting time to recurrence. This will help improve prognostication and inform patient selection for RT.