Walton Centre

Double seronegative NMOSD (DS-NMOSD) lacks approved disease-modifying treatments, and limited data exist on optimal relapse-prevention strategies. In this multicenter, international, retrospective cohort study, we sought to compare the real-world effectiveness of anti-CD20 agents vs nonspecific immunosuppressants as disease-modifying strategies for relapse prevention in DS-NMOSD. A retrospective cohort database was constructed using standardized data collection from medical records across collaborating centers in the United States, Brazil, the United Kingdom, Thailand, Turkiye, and China. Patients meeting IPND-2015 NMOSD criteria with negative serum aquaporin-4 and myelin oligodendrocyte glycoprotein antibody testing via cell-based assays and at least 12 months of follow-up were reviewed. The primary outcome was the incidence rate ratio (IRR) of relapses; secondary outcomes included the annualized relapse rate (ARR) and time to relapse. A total of 103 patients with DS-NMOSD met study criteria, with a median follow-up of 6 years. Anti-CD20 therapy was associated with a significantly lower IRR (0.02, 95% CI 0.01-0.04) and ARR (0.17, 95% CI 0.07-0.40) compared with nonspecific immunosuppressants (0.76, 95% CI 0.40-1.43) after adjusting for covariates. Survival analysis demonstrated a prolonged relapse-free interval with anti-CD20 agents. Our findings support the use of B-cell depletion as a potentially superior relapse-prevention strategy in DS-NMOSD, highlighting its potential as a first-line therapy. This study provides Class IV evidence that, in patients with DS-NMOSD, treatment with a DMT reduces relapse incidence rate ratio compared with no treatment and anti-CD20 DMTs are associated with a lower relapse incidence rate ratio compared with nonspecific immunosuppressants.

Empathic communication is essential for high-quality healthcare, yet patients must often interpret subtle and ambiguous interpersonal cues during healthcare encounters. In such contexts, prior experiences and cognitive-affective processes may shape interpretations in biased ways. In Fibromyalgia Syndrome (FMS), a frequently stigmatised and 'invisible' condition, such biases may influence how patients perceive unclear messages from healthcare professionals. While interpretation bias for pain-related information has been explored, bias in interpreting social-emotional information has not. This study investigated interpretations of ambiguous social-emotional cues from healthcare professionals in individuals with FMS (n = 65), compared with those with other chronic pain conditions (n = 51) and pain-free controls (n = 77). Participants completed a novel scenario-based task assessing the perceived likelihood of positive, neutral, and negative interpretations of ambiguous clinical situations. Validated self-report measures of psychological distress and perceived clinical empathy were also administered. Results showed that individuals with FMS were significantly more likely to endorse negative interpretations and less likely to endorse positive ones relative to both comparison groups, even after controlling for depression, anxiety, and stress. The FMS group also reported greater psychological distress and lower perceived empathy. Moreover, negative interpretation bias was associated with greater distress and lower perceived clinical empathy, while positive bias showed the opposite pattern. These findings suggest that individuals with FMS interpret ambiguous healthcare communication through a distinct cognitive-affective lens. This highlights that patient-provider interactions are not experienced uniformly across chronic pain populations, and that interpretative biases should be considered to improve healthcare communication. PERSPECTIVE: We explored how individuals with fibromyalgia (compared to other chronic pain and pain-free groups) interpret empathy-related ambiguous cues from healthcare professionals. Controlling for psychological distress, the fibromyalgia group showed a stronger negative interpretation bias than both comparison groups. Understanding these socio-cognitive patterns may help improve communication and empathy in fibromyalgia care.

Target trial emulation (TTE) has emerged as a methodological framework to strengthen causal inference from observational health data when randomised controlled trials are infeasible. The credibility of TTE studies depends not only on rigorous design and transparent reporting, but also on their relevance and acceptability to patients and the public. Patient and public involvement and engagement (PPIE) has been shown to enhance the relevance, transparency and impact of health research by shaping research priorities, informing study design and ensuring outcomes reflect patient perspectives. However, the extent to which PPIE has been incorporated into TTE studies remains unclear. This scoping review aims to systematically map the use and reporting of PPIE in published TTE studies. This review will follow the Joanna Briggs Institute methodology for scoping reviews and will be reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Reviews checklist. We will search MEDLINE (Ovid) and Embase (Ovid) from January 2011 to present, limited to English-language publications. Eligible studies will be studies that self-identify as using the TTE framework and report empirical analyses of health outcomes using observational or trial data. We will exclude protocols, methodological or simulation-only studies, preprints, conference abstracts and grey literature. Three reviewers will independently screen titles and abstracts, and then full texts, with disagreements resolved by discussion or adjudication. Data extraction will include study characteristics and PPIE information guided by the Guidance for Reporting Involvement of Patients and the Public 2-Short Form checklist. Findings will be summarised using descriptive statistics, tables, figures and narrative synthesis. Ethics approval is not required, as this review will use publicly available data. Results will be disseminated through a peer-reviewed publication and presented at conferences.

Background: Although multiple sclerosis (MS)-associated tremor and ataxia are well described in the neurological literature, other extrapyramidal movement disorders (MDs), including Holmes tremor, dystonia, chorea, myoclonus, parkinsonism, and restless legs syndrome, have received far less attention and are generally regarded as rare manifestations of MS. Rationale: Although MS is traditionally considered a white matter disease, increasing evidence has demonstrated clinically relevant grey matter involvement, particularly within the basal ganglia, thalamus, and cerebellar–brainstem pathways. Understanding extrapyramidal MDs in MS may therefore provide important insights into the functional networks disrupted by demyelination and inflammation. Aim: This review aims to highlight the available literature on extrapyramidal MDs in MS, outlining their clinical presentations, lesion correlates, and proposed mechanisms. We examined reported cases, reviews, and findings in the literature explaining these disorders and their occurrence in association with acute relapses, as well as their development during the progressive phase of MS. Conclusions: By integrating clinical and pathophysiological evidence, this review highlights how rare extrapyramidal MDs may reflect underlying grey matter pathology and network-level disruption, with potential implications for diagnosis, monitoring, and treatment.

a:2:{s:4:"lang";s:2:"en";s:7:"content";s:1383:"<h3></h3> Whilst brain biopsy is routinely used in the diagnosis of suspected CNS neoplastic disease, its role in the management of suspected non-neoplastic cryptogenic disease, is less clear. This retrospective, single centre study aims to evaluate the diagnostic utility of brain biopsy in this patient population. 59 eligible patients were identified and information regarding the demographics, clinical presentation, eventual diagnosis and management were reviewed. The most common clinical presentations were focal neurological deficit (66%) followed by encephalopathy (39%). A majority (64.4%) had a targeted biopsy based on radiological abnormalities. Our results demonstrated that brain biopsy provided a definitive diagnosis in 52.5% of cases. Of the diagnostic biopsies, neuroinflammatory disease (45.2%) and primary CNS neoplasm (41.9%) were the most common diagnoses reported. 17% of patients experienced complications from the procedure, with seizures counting for the majority of these complications. These findings align with other studies reporting similar diagnostic outcomes and emphasise the clinical value of brain biopsy in suspected non-neoplastic neurological diseases. The study supports the continued use of brain biopsy as a useful tool in managing patients with cryptogenic neurological disease. Shika.Habershon{at}rlbuht.nhs.uk ";}

BackgroundDeficits of emotion recognition have received increasing attention in people with Huntington's disease (HD) in the three decades since the discovery of the HD gene. However, the characterisation of such deficits across different disease stages, types of stimuli, and sensory modalities is currently unclear.ObjectiveThis study aimed to provide a comprehensive review of the evidence on emotion recognition deficits in HD gene carriers (both manifest and premanifest) over the three decades since definitive gene testing.MethodA systematic review was carried out from January 1993 to January 2025 across MEDLINE, PsycINFO, Academic Search Complete, and CINAHL (PROSPERO registration: CRD42023398649).ResultsFrom 9735 initial citations, 59 studies were eventually included. In manifest HD, facial recognition of negative emotions such as anger, fear, disgust, and sadness was consistently impaired, whereas happiness and neutral expressions were generally spared. A few auditory studies showed consistent deficits for disgust, fear, and anger, while happiness and sadness appeared less affected. Only preliminary evidence is currently available for deficits involving body language, visual and written vignettes, videos, and olfactory and gustatory tasks. Although sparser, the evidence for premanifest HD suggests that some individuals may develop significant recognition difficulties prior to motor onset, particularly due to early frontostriatal deterioration and white matter disruption.ConclusionsImpairments of facial recognition of negative emotions are reported consistently in manifest HD, while only preliminary results are available for other modalities. The evidence involving premanifest HD is much sparser. Key implications for clinical practice and future research are outlined and discussed.

ABSTRACT Introduction Neuromyelitis optica spectrum disorder (NMOSD) is a rare, relapsing autoimmune disorder of the central nervous system, characterized by inflammatory attacks affecting the optic nerves, spinal cord and brain. In most cases, pathogenic antibodies against aquaporin-4 (AQP4-IgG) are detectable. These antibodies target astrocytes, triggering complement activation and the release of proinflammatory cytokines such as interleukin-6 (IL-6), culminating in an astrocytopathy and neurological disability. Areas covered In this review, Medical Subject Heading (MeSH) and related entry terms were used to search English literature in PubMed and ClinicalTrial.gov databases, respectively. MeSH included but were not limited to Neuromyelitis optica (NMO), Neuromyelitis Optica Spectrum Disorders (NMOSD), pathogenesis, complement, immune cells, B-cell, T-cell, cytokines, and therapy. Expert opinion Over the past decade, significant strides in our understanding of NMOSD immunopathogenesis have led to the development of targeted therapies that have revolutionized patient outcomes and survival. This review outlines the clinical features of NMOSD and examines current and emerging therapeutic strategies in the context of disease biology. It also addresses ongoing challenges, including optimization of acute attack management, strategies for treatment de-escalation, and prospects for achieving immune tolerance.

ObjectiveThis study aims to determine the outcomes of nickel allergic patients who underwent a trial of forearm arterial stenting with a nickel-based stent, with follow-up to assess for an allergic reaction. In the absence of adverse effects, patients had their intracranial aneurysm treatment with a nickel-based cerebrovascular device.MethodsA retrospective analysis was performed on patients who had an allergy to nickel, with an intracranial aneurysm who underwent treatment with a permanently implanted nickel-containing device. Nickel allergy was established by clinical history and dedicated patch testing. Outcomes such as in-stent thrombosis or any intracranial complications were recorded.ResultsOver a 10-year period, there were 18 patients who had a peripheral stent without development of in-stent stenosis, thrombosis or occlusion. One patient developed a cutaneous allergic reaction to the peripheral stent and their intracranial procedure was with a nitinol-free device.Of 17 patients who underwent intracranial treatment with a nitinol device, there was one patient who developed a postoperative complication of fish-mouthing of the device which has been reported in patients with a nickel contact allergy, but further studies are warranted to establish a causative relationship. Another patient omitted prescribed antiplatelet medication and occluded their stent. The remaining fifteen patients developed no complications with aneurysm occlusion on imaging.ConclusionPatients with a nickel allergy who would be eligible for endovascular treatment could benefit from trial peripheral arterial stenting. This provides an alternative approach to avoid unnecessarily eliminating endovascular treatment options with nickel-containing devices from which these patients may potentially still benefit.

Abstract Background 50-80% of all glioma patients will have seizures. Guidelines recommend against prophylactic anti-seizure medication, but levetiracetam is frequently prescribed. Our aim was to determine the effectiveness of 12-months prophylactic levetiracetam at reducing seizure risk. Methods Seizure-naïve patients undergoing glioma surgery were randomised (1:1) to 12-months levetiracetam or no prophylaxis and followed until death or maximum 18-months. The primary outcome was one-year risk of first seizure. Patients who died within 12-months of randomisation without experiencing a seizure were excluded from the primary outcome analysis. Target accrual was 804 participants. The trial was registered ( ISRCTN 49474281 and EudraCT 2018-001312-30). Results Between Oct 10, 2019 and Aug 30, 2022, 96 patients, from 24 to 79 years of age, were randomised to levetiracetam (n=49) or no prophylaxis (n=47). The trial closed early due to slow accrual and the Covid pandemic. In the levetiracetam group 17 patients had a seizure and 32 did not (19 survived ≥ 12-months, 13 died within 12-months). In the no prophylaxis group 15 patients had a seizure and 30 did not (21 survived ≥12-months, 9 died within 12-months). Seventeen of the 36 evaluable levetiracetam patients (47%) had a seizure, compared with 15 of 36 evaluable no prophylaxis patients (41%) (OR 1.25, 95%CI 0.49-3.21, p=0.64). There were no levetiracetam related serious adverse events. Conclusions The SPRING trial provides no evidence of a difference between levetiracetam and no prophylaxis in the 12-month seizure risk in patients undergoing glioma surgery, but the study was underpowered. The role of prophylactic anti-seizure medication remains undefined.