UCL Biomedical Research Centre

Functional neurological disorder (FND) commonly arises in the context of injury, trauma, or litigation and poses distinctive medicolegal challenges. This review outlines how positive clinical signs and contemporary neurobiological models support FND as a robust diagnosis, while distinguishing it from factitious disorder and malingering. We discuss approaches to assessing authenticity of reported disability, the role and limitations of symptom and performance validity tests, and the pitfalls of equating inconsistency with deception. We then consider causation within common legal frameworks using a predisposing-precipitating-perpetuating model to analyze the contribution of index events, background vulnerabilities, and the litigation process itself. Finally, we summarize current evidence on treatment and prognosis, highlighting the limits of prediction and the need to offer courts transparent, probabilistic opinions on long-term outcome and care needs. Our aim is to support clinicians in providing balanced, clinically grounded expert evidence for patients with FND.

To describe the clinical findings and report the incidence of patients developing non-infectious intraocular inflammation (IOI) following intravitreal faricimab injections (IVFs). A retrospective review of electronic medical records was conducted for patients receiving faricimab intravitreal injections for neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO) at Moorfields Eye Hospital, London, United Kingdom, over a 24-month period. 3985 eyes from 3151 patients were included and underwent a total of 28,535 IVFs (20,982 for nAMD, 7553 for DMO). 57 eyes from 46 patients presented at least one episode of IOI. The 2-year estimated incidence of IOI was 0.20% [95% CI 0.15-0.26] per injection, 1.43% [95% CI 1.08-1.85] per eye and 1.46% [95% CI 1.07-1.94] per patient. Mean visual acuity (VA) was significantly different between the day of IVF (0.48 ± 0.43 logMAR, range: 0-1.8) and the day of IOI diagnosis (0.67 ± 0.52, range: 0-2.3) (p < 0.001). VA after IOI resolution showed no significant difference from baseline (p > 0.99). Intravitreal injections were resumed in 42 eyes. IVFs re-challenge was attempted in 9 eyes, with 5 developing another episode of IOI. This study describes one of the largest reported cohorts of IOI cases following faricimab treatment. It confirms that the incidence of IOI is rare and aligns with the rates of IVF-related adverse effects reported in clinical trials and in recent real-world studies. Overall, faricimab demonstrated a favourable safety profile with good prognosis in cases of IOI.

To explore associations of clinic and 24-hour ambulatory blood pressure (BP) monitoring (ABPM) with cardiovascular death (CVD), parameters were modeled for age and sex in this large cohort in primary care. In the Spanish ABPM Registry, 59.124 patients had complete data on mortality, age, sex, and all ABPM. Office, mean, 24-hour, daytime, and nighttime systolic BP (SBP), diastolic BP, and pulse pressure (PP) were related to CVD according to age and sex and were modelled with restricted cubic splines to get trajectories. During a median of 9.7 years, 2361 patients had CVD (1229 males, 1132 females). Nonlinear relationships for office, 24-hour mean, daytime, and nighttime SBP, diastolic BP, and PP (P<0.0001 for all) for both sexes were observed. Until 75 years, SBP was higher in males than females, but differences were minimized after ≈60 to 70 years (P for interaction <0.0001). High SBP and PP are associated with CVD without heterogeneity between sexes and across aging. The increase of SBP and PP was higher at a higher age for females than males (P for interaction <0.0001). CVD was age-dependent, and ABPM, in particular nighttime BP did more closely associated with risk than office BP in younger than in older individuals. Twenty-four-hour mean, nighttime BP, and PP were closely associated with risk being higher in elderly females than males after 75 years, corresponding to a rise in BP in older females. Guidelines should continue to mandate the evaluation of 24-hour ABPM data for risk prediction.

Computed tomography-based fractional flow reserve computation (CT-FFR) is widely used in clinical practice, based on its efficacy demonstrated in many studies. However, major assumptions remain with the outflow boundary conditions (BCs) representing coronary microvasculature, especially in hyperaemia. We here propose a novel method to estimate patient-specific microvascular response to hyperaemia for CT-FFR calculations, based on patients' routinely available demographic data. A statistical model to predict microvascular flow response (MFR) from routinely collected patient demographic parameters was derived using PET-based perfusion data of 101 patients with coronary artery disease. CT-FFR computations were then conducted with patient-specific anatomical models and outflow BCs derived from various MFR models including the proposed approach. The FFR values were calculated for an independent test cohort of 10 patients who had undergone CT coronary angiography, CT perfusion imaging and invasive FFR measurement. Computed FFR values were compared against invasive FFR and other CT-FFR algorithms. A multivariate regression model predicting patient-specific MFR was derived as a function of sex, diabetes and smoking status of the patient. FFR values computed using our model agreed well with the invasive FFR (0.76 ± 0.09 vs. 0.75 ± 0.10, P = 0.217). The FFRs predicted with our model were also comparable to those calculated using outflow BC tuned with patient-specific perfusion data (FFR: 0.74 ± 0.10, P = 0.233 vs. invasive FFR) and showed marked improvement over the conventional approach (FFR: 0.68 ± 0.11, P = 0.004 vs. invasive FFR). Diagnostic accuracy vs. invasive FFR were 100, 91 and 82% for CT-FFR with CTP-based MFR, demography-based MFR, and conventional approach, respectively. The proposed demography-based MFR model significantly improves FFR computation accuracy compared with a typical conventional model that assumes constant, healthy and population average MFR. Although its diagnostic accuracy is slightly lower than that of CT-FFR calibrated with patient-specific perfusion imaging data (91 vs. 100%), the demography-based model offers a substantial practical advantage by not requiring additional non-standard data acquisition, such as perfusion imaging. Consequently, it shows strong potential as a practical enhancement to conventional CT-FFR algorithms.

Istradefylline, a selective adenosine A2A receptor antagonist, is approved as an adjunct to levodopa in Parkinson's disease, but its long-term effects on clinically meaningful outcomes are unclear. We aimed to compare the association of istradefylline versus catechol-O-methyltransferase (COMT) inhibitors with mortality, treatment escalation, and disease progression in levodopa-treated Parkinson's disease. We conducted a nationwide cohort study emulating a target trial using the DeSC claims database in Japan. Patients aged ≥50 years with levodopa-treated Parkinson's disease between 2014 and 2023 were included. Strategies were initiation of istradefylline versus COMT inhibitors. Primary outcomes were all-cause mortality, levodopa-equivalent daily dose (LEDD) escalation to ≥1100mg, and dementia or psychosis. Secondary outcomes were fractures, cardiovascular events, pneumonia, and depression. Intention-to-treat and per-protocol effects were estimated using Cox models with propensity score-based overlap weighting. We identified 3190 istradefylline and 7986 COMT inhibitor initiators. In intention-to-treat analysis, istradefylline was associated with lower risks of mortality (hazard ratio [HR] 0.91; 95% CI 0.84-0.99) and LEDD escalation (HR 0.83; 95% CI 0.73-0.94). Associations were stronger in per-protocol analysis (mortality: HR 0.84, 95% CI 0.72-0.97; LEDD escalation: HR 0.71, 95% CI 0.59-0.84). Istradefylline was linked to higher fracture risk (intention-to-treat HR 1.13, 95% CI 1.02-1.25; per protocol HR 1.23, 95% CI 1.07-1.41). No differences were observed for dementia, psychosis, or other outcomes. Istradefylline was associated with reduced mortality and treatment escalation but increased fracture risk compared with COMT inhibitors, supporting further evaluation of adenosine A2A antagonists.

Abstract Fast-ripples have been proposed as a promising biomarker in epilepsy, but their specificity remains unclear. In particular, it is uncertain whether they reflect chance coincident neural activity or distinctly generated pathological entities. We combined in silico simulations, neuronal cultures, a rodent model of hippocampal epilepsy, and human microwire recordings to investigate whether fast-ripples occur more frequently than expected by the chance aggregation of action potentials. Our simulations showed that chance aggregation can generate fast-ripples and predicted higher occurrence during wakefulness, which was confirmed in rodent recordings. The likelihood of exceeding chance depended on biological system complexity and vigilance state: fast-ripples in neuronal cultures did not surpass chance, whereas those in awake – but not sleeping – rodents did. Similarly, the frequency of fast-ripples in awake human recordings was ∼30% greater than expected by chance. As such, our findings suggest that most fast-ripples reflect stochastic network activity rather than distinctly generated pathological entities, challenging prevailing assumptions about their pathogenesis and biomarker specificity.

Robotic-assisted systems are being increasingly integrated into orthopaedic surgery, offering potential improvements in precision, reproducibility, and patient-reported outcome measures (PROMs) for unicompartmental knee arthroplasty (UKA), total knee arthroplasty (TKA), and total hip arthroplasty (THA). A review and summary of the early value assessment (EVA) undertaken by the National Institute for Health and Care Excellence (NICE) to evaluate the clinical effectiveness, cost-effectiveness, and implementation considerations of these technologies is presented. The EVA includes a review of the literature, an evidence gap analysis, and an evidence generation plan. Evidence from 28 studies and two registries suggested that robotic-assisted surgery was noninferior to conventional approaches in key outcomes, including PROMs, complications, hospital stay, and revisions, but it was associated with enhanced implant alignment. Short-term PROMs showed modest improvements, although most differences fell below currently defined clinically meaningful thresholds. Revision data were limited in follow-up, and ergonomic benefits for surgeons were uncertain. Economic evaluations suggested potential cost-effectiveness, particularly for THA, but assumptions regarding utilities, resource use, procedure volume, and implant costs introduced substantial uncertainty. The EVA highlighted the importance of training, equitable access, and national coordination for implementation. Evidence gaps were identified in long-term revision rates, health-related quality of life outcomes, productivity, sub-group effects, surgical team benefits, and learning curves. NICE recommended conditional adoption of six robotic platforms (ApolloKnee (Corin, UK), CORI (Smith & Nephew, UK), Mako (Stryker, USA), ROSA (Zimmer Biomet, USA), SkyWalker (MicroPort, China), and VELYS (DePuy Synthes, USA)) over a three-year evidence generation period, requiring annual reporting and adherence to regulatory standards. While robotic-assisted arthroplasty offers technical advantages, definitive clinical and economic benefits remain unproven. Surgeons, healthcare systems, and industry partners will need to work collaboratively to provide the required evidence in the next three years. A UK robotic registry could help address the evidence gaps more rapidly than individual centres by capturing large-scale national data.

The MOLES scoring system was developed to help non-experts estimate the likelihood of malignancy in melanocytic choroidal tumours according to mushroom shape, orange pigment, large size, enlargement, and subretinal fluid. If only imaging is assessed, as in telemedicine, a choroidal melanoma (CM) may be scored as a naevus if subretinal fluid and orange pigment are not evident and if sequential imaging is not available. In such a telemedicine environment it might be safest to modify the MOLES score to assume lesion enlargement has occurred if the thickness and/or diameter exceed 3 mm or 7.5 mm, respectively. Clinical records and multimodal imaging of patients with clinically diagnosed small CM (with no histopathological analysis) treated with ruthenium-106 (Ru-106) plaque brachytherapy were retrospectively reviewed. Sensitivity of the original and revised MOLES in estimating likelihood of malignancy were evaluated. The cohort comprised 142 patients (mean age 60 ± 13.6 years) with small CM. Mean tumour thickness and largest basal diameter (LBD) were 1.9 ± 0.5 mm (range 0.4-2.5 mm) and 7.5 ± 1.9 mm (range 3.5-15 mm), respectively. The MOLES score was ≥3 in 97.9% and 100% of small CM according to the original and modified scoring systems, respectively. No cases had MOLES score <2, indicating that 100% of patients would have been referred for specialist assessment. The revised MOLES score increases sensitivity in diagnosing CM from 97.9% to 100% and is therefore a useful aid to patient management.