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PurposeMultiple sclerosis (MS) is a chronic neurological condition that affects approximately 150 000 people in the UK and presents a significant healthcare burden, including the high costs of disease-modifying treatments (DMTs). DMTs have substantially reduced the risk of relapse and moderately reduced disability progression. Patients exhibit a wide range of responses to available DMTs. The Predicting Optimal INdividualised Treatment response in MS (POINT-MS) cohort was established to predict the individual treatment response by integrating comprehensive clinical phenotyping with imaging, serum and genetic biomarkers of disease activity and progression. Here, we present the baseline characteristics of the cohort and provide an overview of the study design, laying the groundwork for future analyses.ParticipantsPOINT-MS is a prospective, observational research cohort and biobank of 781 adult participants with a diagnosis of MS who consented to study enrolment on initiation of a DMT at the Queen Square MS Centre (National Hospital of Neurology and Neurosurgery, University College London Hospital NHS Trust, London) between 01/07/2019 and 31/07/2024. All patients were invited for clinical assessments, including the expanded disability status scale (EDSS) score, brief international cognitive assessment for MS and various patient-reported outcome measures (PROMs). They additionally underwent MRI at 3T, optical coherence tomography and blood tests (for genotyping and serum biomarkers quantification), at baseline (i.e., within 3 months from commencing a DMT), and between 6–12 (re-baseline), 18–24, 30–36, 42–48 and 54–60 months after DMT initiation.Findings to date748 participants provided baseline data. They were mostly female (68%) and White (75%) participants, with relapsing–remitting MS (94.3%), and with an average age of 40.8 (±10.9) years and a mean disease duration of 7.9 (±7.4) years since symptom onset. Despite low disability (median EDSS 2.0), cognitive impairment was observed in 40% of participants. Most patients (98.4%) had at least one comorbidity. At study entry, 59.2% were treatment naïve, and 83.2% initiated a high-efficacy DMT. Most patients (76.4%) were in either full- or part-time employment. PROMs indicated heterogeneous impairments in physical and mental health, with a greater psychological than physical impact and with low levels of fatigue. When baseline MRI scans were compared with previous scans (available in 668 (89%) patients; mean time since last scan 9±8 months), 26% and 8.5% of patients had at least one new brain or spinal cord lesion at study entry, respectively. Patients showed a median volume of brain lesions of 6.14 cm3, with significant variability among patients (CI 1.1 to 34.1). When brain tissue volumes z-scores were obtained using healthy subjects (N=113, (mean age 42.3 (± 11.8) years, 61.9% female)) from a local MRI database, patients showed a slight reduction in the volumes of the whole grey matter (−0.16 (−0.22 to –0.09)), driven by the deep grey matter (−0.47 (−0.55 to –0.40)), and of the whole white matter (−0.18 (−0.28 to –0.09)), but normal cortical grey matter volumes (0.10 (0.05 to 0.15)). The mean upper cervical spinal cord cross-sectional area (CSA), as measured from volumetric brain scans, was 62.3 (SD 7.5) mm2. When CSA z-scores were obtained from the same healthy subjects used for brain measures, patients showed a slight reduction in CSA (−0.15 (−0.24 to –0.10)).Future plansModelling with both standard statistics and machine learning approaches is currently planned to predict individualised treatment response by integrating all the demographic, socioeconomic, clinical data with imaging, genetic and serum biomarkers. The long-term output of this research is a stratification tool that will guide the selection of DMTs in clinical practice on the basis of the individual prognostic profile. We will complete long-term follow-up data in 4 years (January 2029). The biobank and MRI repository will be used for collaborative research on the mechanisms of disability in MS.

Background Optical Coherence Tomography (OCT) imaging is being increasingly used in clinical practice for the monitoring of papilloedema. The aim is to characterise the extent and location of the Retinal Nerve Fibre Layer (RNFL) Thickness automated segmentation error (SegE) by manual refinement, in a cohort of Idiopathic Intracranial Hypertension (IIH) patients with papilloedema and compare this to controls. Methods Baseline Spectral Domain OCT (SDOCT) scans from patients with IIH, and controls with no retinal or optic nerve pathology, were examined. The internal limiting membrane and RNFL thickness of the most severely affected eye was examined for SegE and re-segmented. Using ImageJ, the total area of the RNFL thickness was calculated pre and post re-segmentation and the percentage change was determined. The distribution of RNFL thickness error was qualitatively assessed. Results Significantly greater SegE ( p  = 0.009) was present in RNFL thickness total area, assessed using ImageJ, in IIH patients ( n  = 46, 5% ± 0–58%) compared to controls ( n  = 14, 1% ± 0–6%). This was particularly evident in moderate to severe optic disc swelling ( n  = 23, 10% ± 0–58%, p  < 0.001). RNFL thickness was unable to be quantified using SDOCT in patients with severe papilloedema. Conclusions SegE remain a concern for clinicians using SDOCT to monitor papilloedema in IIH, particularly in the assessment of eyes with moderate to severe oedema. Systematic assessment and manual refinement of SegE is therefore important to ensure the accuracy in longitudinal monitoring of patients.

IntroductionPeople with multiple sclerosis (pwMS) receiving B-cell depleting disease-modifying therapy (BCD-DMT) are vulnerable to severe COVID-19. Data on vaccine immunogenicity in this patient group are incomplete. In the context of the rapid evolution of SARS-CoV-2 2020–22, we compared vaccine responses in pwMS and healthy vaccinated adults (HVA) after three doses of messenger RNA vaccine encoding Ancestral SARS-CoV-2 Spike.MethodsIn this prospective observational cohort study, we collected serum from 226 pwMS prevaccine and postvaccine and quantified neutralising antibody titres (nAbT) in a high-throughput live virus assay against SARS-CoV-2 Ancestral, Alpha, Delta, Omicron BA.1, BA.2 and BA.5. We compared nAbT in pwMS and HVA, matched by age, sex, vaccine type, number of doses and time since exposure, using Wilcoxon signed-rank and χ2 tests. We further investigated nAbT vaccine response in pwMS on BCD-DMTs or non-depleting DMTs.ResultsPrior to third vaccination, nAbTs against nearly all variants tested were significantly lower (p<0.05) in pwMS taking BCD therapy than those in HVA or B-cell replete pwMS, and were not significantly boosted following vaccination. In contrast, B-cell replete pwMS versus HVAs exhibited equivalent prevaccination nAbTs against all variants, which were comparably boosted against most variants following vaccination. Consequently, differences in nAbTs against all variants tested were further magnified between B-cell replete and B-cell depleted pwMS post-third vaccination. Across the entire cohort, there were no COVID-19 hospitalisations or deaths. Notably, sera collected prior to the pandemic from pwMS demonstrated pre-existing, pan-coronavirus neutralising activity against seasonal HCoV-OC43 and SARS-CoV-2 variants.ConclusionsPwMS taking BCD therapy have limited antibody boosting following repeated COVID-19 vaccination. However, the absence of severe outcomes in pwMS, despite reduced immunogenicity, suggests a lower threshold for effective protection than previously reported. These findings support more nuanced risk stratification in clinical policy.

BackgroundIn the acute setting, performance of a targeted neurological examination by non-neurologists prior to referral is an expected standard of care.AimsThe aims were to characterise the reasons for acute neurology service referral and determine the percentage of neurological examinations including fundoscopy performed by non-neurologists prior to acute neurology input.MethodsConsecutive referrals to the acute neurology service at two hospital sites over a four-month period in 2024 were analysed. An expected standard of documented neurological examination prior to specialist referral was created and independently verified by a panel of neurology consultants.ResultsOf 232 referrals across two hospital sites, 39.3% had a targeted neurological examination documented, 10% had no documented neurological examination and 9% had only GCS or pupillary reflexes documented. For lower limb examinations, deep tendon reflexes were the least commonly performed component, documented in 35% of referrals. Of the referrals that qualified for fundoscopy assessment (n=43), an examination was documented in 16%. Seizures were the most common reason for referral (19.8%).DiscussionThis audit highlights that the majority of acute neurology referrals lacked a documented neurological examination. Future efforts will include identifying and overcoming real and perceived barriers to performing a neurological examination amongst non-neurologists.a.aojula@nhs.net

Neurophobia is well documented amongst medical students. However, teaching resources that may address neurophobia have been poorly evaluated. Our brief neurological examination video was deemed a useful teaching resource by neurologists (Hassan-Smith et al., JNNP, 2016) and has been viewed >1 00 000 times via YouTube. However, this study aimed to evaluate the impact of the same examination video on the level of neurophobia amongst 4th year medical students.MethodBoth our control (n=51) and intervention (n=65) groups received a curriculum based neurology induction lecture (3x between Sept 2016-Feb 2017). Additionally, during the lecture, the intervention group were exposed to the brief neurological examination video that discussed the reasoning behind the neurological examination, relevant neuroanatomy and common neurological signs. The level of neurophobia was subjectively assessed at baseline and post lecture using a modified version of the validated CSLP084 questionnaire (Schon et al) via an electronic voting system.ResultsWe will be presenting our findings on the impact of the brief neurological examination video on the confidence levels of medical students to perform the neurological examination and illicit signs of neurological disease. Implementation of our brief neurological examination video, available via the @TOSSTUDYGroup twitter feed, into the medical school curriculum has the potential to reduce neurophobia amongst students.

BackgroundThe use of diffusion tensor imaging (DTI) to examine Decorin's ability to prevent cerebral cytopathology in communicating hydrocephalus is yet to be fully investigated. Hence, this study aimed to determine whether Decorin treatment influences alterations in DTI parameters and cytopathology in an experimental model of the disease.MethodAccordingly, communicating hydrocephalus was induced by injecting Kaolin into the basal cisterns in 3-week old rats followed immediately by 14 days of continuous intraventricular delivery of either human recombinant Decorin (n=5) or vehicle (n=6). At 14-days post-kaolin, just prior to sacrifice, DTI was conducted. Myelin integrity (myelin basic protein), gliosis (glial fibrillary acidic protein, GFAP) and aquaporin-4 levels were evaluated by immunohistochemistry in the same seven cerebral structures analysed by DTI.ResultsDecorin significantly decreased myelin damage in the caudal internal capsule and prevented caudal periventricular white matter oedema and astrogliosis. Furthermore, Decorin treatment prevented an increase in caudal periventricular white matter mean diffusivity (p=0.032) as well as caudal corpus callosum axial diffusivity (p=0.004) and radial diffusivity (p=0.034). Furthermore, DTI parameters correlated primarily with periventricular white matter GFAP and aquaporin-4 levels.ConclusionOverall, these findings suggest that Decorin has the therapeutic potential to reduce white matter cytopathology in communicating hydrocephalus.

Background In an effort to develop novel treatments for communicating hydrocephalus, we have shown previously that the transforming growth factor-β antagonist, decorin, inhibits subarachnoid fibrosis mediated ventriculomegaly; however decorin’s ability to prevent cerebral cytopathology in communicating hydrocephalus has not been fully examined. Furthermore, the capacity for diffusion tensor imaging to act as a proxy measure of cerebral pathology in multiple sclerosis and spinal cord injury has recently been demonstrated. However, the use of diffusion tensor imaging to investigate cytopathological changes in communicating hydrocephalus is yet to occur. Hence, this study aimed to determine whether decorin treatment influences alterations in diffusion tensor imaging parameters and cytopathology in experimental communicating hydrocephalus. Moreover, the study also explored whether diffusion tensor imaging parameters correlate with cellular pathology in communicating hydrocephalus. Methods Accordingly, communicating hydrocephalus was induced by injecting kaolin into the basal cisterns in 3-week old rats followed immediately by 14 days of continuous intraventricular delivery of either human recombinant decorin (n = 5) or vehicle (n = 6). Four rats remained as intact controls and a further four rats served as kaolin only controls. At 14-days post-kaolin, just prior to sacrifice, routine magnetic resonance imaging and magnetic resonance diffusion tensor imaging was conducted and the mean diffusivity, fractional anisotropy, radial and axial diffusivity of seven cerebral regions were assessed by voxel-based analysis in the corpus callosum, periventricular white matter, caudal internal capsule, CA1 hippocampus, and outer and inner parietal cortex. Myelin integrity, gliosis and aquaporin-4 levels were evaluated by post-mortem immunohistochemistry in the CA3 hippocampus and in the caudal brain of the same cerebral structures analysed by diffusion tensor imaging. Results Decorin significantly decreased myelin damage in the caudal internal capsule and prevented caudal periventricular white matter oedema and astrogliosis. Furthermore, decorin treatment prevented the increase in caudal periventricular white matter mean diffusivity (p = 0.032) as well as caudal corpus callosum axial diffusivity (p = 0.004) and radial diffusivity (p = 0.034). Furthermore, diffusion tensor imaging parameters correlated primarily with periventricular white matter astrocyte and aquaporin-4 levels. Conclusions Overall, these findings suggest that decorin has the therapeutic potential to reduce white matter cytopathology in hydrocephalus. Moreover, diffusion tensor imaging is a useful tool to provide surrogate measures of periventricular white matter pathology in communicating hydrocephalus.