The UCL Queen Square Institute of Neurology is an institute within the Faculty of Brain Sciences of University College London (UCL) and is located in London, United Kingdom. Together with the National Hospital for Neurology and Neurosurgery, an adjacent facility with which it cooperates closely, the institute forms a major centre for teaching, training and research in neurology and allied clinical and basic neurosciences.The institute has a staff of around 710 and 500 graduate students, an annual turnover of £81million and occupies around 12,000 sq m of laboratory and office space. Four of the 12 most highly cited authors in neuroscience and behaviour in the world are currently based at the institute. The institute conducts research into a wide range of neurological diseases, including movement disorders, multiple sclerosis, epilepsy, brain cancer, stroke and brain injury, muscle and nerve disorders, cognitive dysfunction and dementia. It forms a key part of UCL Neuroscience.
Background and Objectives The 2024 McDonald criteria provide new recommendations for multiple sclerosis (MS) diagnosis, but validation of the criteria is lacking. We wanted to investigate the application and performance of the 2024 McDonald criteria in patients with suspected MS seen in routine clinical practice. Methods We retrospectively identified patients referred with clinical and/or radiologic suspicion for MS between January and December 2024. All patients had a minimum diagnostic evaluation with brain and spinal cord MRI. The 2017 McDonald criteria were applied prospectively, and the 2024 McDonald criteria were applied retrospectively after the initial diagnostic workup and at last follow-up. We investigated (1) the number of patients diagnosed with MS using the 2017 McDonald criteria or the 2024 McDonald criteria, and (2) the diagnostic performance of the 2024 McDonald criteria when applied during the initial diagnostic workup, with an MS diagnosis using the 2017 McDonald criteria as the reference-standard. Results In 347 patients (mean age 39.4 years, 66% female) with suspected MS followed up for mean 15.3 (range 8-20) months, 73 (21%) had alternative disorders and were excluded. After applying the 2024 McDonald criteria in the remaining 274 patients, more patients were diagnosed with MS after the initial diagnostic workup (220 vs 172, p < 0.01), and at follow-up (237 vs 204, p < 0.01), compared with the 2017 McDonald criteria, and fewer patients were diagnosed with clinically or radiologically isolated syndrome. The median time to diagnosis was 40 vs 84 days (p < 0.01), respectively. After initial diagnostic workup, the 2024 McDonald criteria demonstrated high sensitivity (92.6%, 95% CI 88.1%-95.8%) and accuracy (83.6%, 95% CI 78.7%-87.8%), for an MS diagnosis using 2017 McDonald criteria at last follow-up, but moderate specificity (57.8%, 95% CI 45.4%-69.4%). The increased rate of MS diagnosis and the diagnostic performance of the revised criteria was similar in children (<18 years) and older adults (>50 years). Discussion Use of the 2024 McDonald allows for earlier MS diagnosis, but also more frequent diagnosis including in patients with radiologically isolated syndrome. The revised criteria have similar performance across the lifespan. Limitations include the lack of data on central vein sign and kappa free light chains, and missing optic nerve assessment in some patients.
GBA1 variants are common genetic risk factors for Parkinson's disease and also for dementia with Lewy bodies. New evidence highlights the relationship between the different GBA1 variants and their associated clinical presentation and disease progression, although penetrance is low and the majority of carriers do not develop a synucleinopathy. The clinical profile of GBA1-associated Parkinson's disease is characterised by a faster rate of progression with more severe cognitive and autonomic dysfunction than idiopathic Parkinson's disease, particularly in those carrying severe pathogenic variants. The mechanisms involved in phenotypic conversion and disease progression in carriers of GBA1 variants are being elucidated, and this knowledge could be translated into clinically relevant biomarker profiles. GBA1 has become a target for intervention for both GBA1-associated Parkinson's disease and idiopathic Parkinson's disease, with therapeutic strategies aiming to prevent or slow disease progression via pharmacological chaperones, enzymatic allosteric activators, metabolic interventions, and modulation of gene expression.
Perseveration - repeating one action when others would generate larger rewards - is a common behavior, but neither its purpose nor neuronal mechanisms are understood. Here we demonstrate a neural correlate and causal role of dorsal prefrontal cortex, specifically anterior secondary motor cortex (MOs) in perseveration in mice performing a dynamic reward learning task. An auditory go cue signaled mice to turn a wheel either left or right, with the reward probability of each action switching in blocks. Mice perseverated, gaining suboptimal reward, but were faster when making repeated choices. Neuropixels recordings found neurons whose activity correlated with perseveration and predicted rapid reaction times, almost exclusively in anterior MOs. Optogenetically inhibiting this region during the choice period reduced perseveration and slowed reactions. In contrast, inactivating medial prefrontal cortex at choice time had no effect, but inactivating it after reward delivery impaired learning. In this task, therefore, anterior MOs reflects a perseverative decision variable, and is necessary for mediating the effect of this decision variable on choice and reaction time.
Despite advances in genomic diagnostics, the majority of individuals with rare diseases remain without a confirmed genetic diagnosis. The rapid emergence of advanced omics technologies, such as long-read genome sequencing, optical genome mapping and multiomic profiling, has improved diagnostic yield but also substantially increased analytical and interpretational complexity. Addressing this complexity requires systematic multidisciplinary collaboration, as recently demonstrated by targeted diagnostic workshops. Here, we highlight the experience of the Solve-RD consortium, a pan-European initiative, in implementing four structured workshops, termed 'Solvathons', as a regular and effective component of its operational workflow. We provide actionable insights, best practices and lessons learned for successful data integration, expert training and scalable collaborative diagnostics within large research consortia.
Efgartigimod is an established therapy for acetylcholine receptor antibody-positive generalized myasthenia gravis, yet real-world data on long-term overall responsiveness, response patterns, steroid-sparing effects, bridging therapy use, and predictors of benefit remain limited. In this multicenter retrospective study, we evaluated 46 patients treated across seven tertiary centers between April 2022 and March 2025, collecting demographic, clinical, therapeutic, and outcome data. Patients received 193 treatment cycles (mean 4.3 per patient) with a mean inter-cycle interval of 9.8 weeks. Following the first cycle, 86.9 % achieved a ≥2-point improvement in the Myasthenia Gravis Activities of Daily Living scale and 43.5 % reached minimal symptom expression (MSE); overall, 52.2 % achieved MSE at least once during follow-up. Nonetheless, 35.9 % discontinued efgartigimod due to insufficient efficacy, underscoring heterogeneous and often non-durable responses. Among 29 patients on prednisone, 58.6 % achieved a significant dose reduction (30.9–16.8 mg/day, p = 0.001), with shorter disease duration predicting successful tapering. Bridging therapy was successful in 5 patients, particularly those receiving azathioprine or mycophenolate (p = 0.040), supporting its utility during transitions to slower-acting immunosuppressants. Adverse events occurred in 21.7 % of patients, were generally mild, and led to discontinuation in only one case. Overall, efgartigimod was effective and well tolerated, but treatment responses varied, and cycle-based regimens frequently failed to sustain benefit. The observed steroid-sparing effect and predictors of response highlight the need for personalized treatment strategies and prospective studies to refine long-term use and optimize patient selection.
