bluuebunny/crossref_metadata_2025_split huggingface dataset:
132 Adverse prognostic factors predicting disease modifying therapies in MS: a real- world cohort
Authors: Cauchi Marija , Harding Katharine , Wynford-Thomas Ray , Pickersgill Trevor , Wardle Mark , Robertson Neil , Tallantyre Emma 
Published: August 2022

BackgroundMultiple sclerosis (MS) demonstrates considerable variability in disease course and prognosis. An improved understanding of factors that predict long-term outcome, particularly early in disease allows for informed, personalised decisions to optimise MS treatment.MethodsData was collected on sequential, newly diagnosed patients from a single MS centre from 2016-2018. Demographic, clinical, and radiological features at disease onset were documented and number of adverse prognostic factors (APF) listed for individual patients. Number and type of APF was then correlated with outcome variables including EDSS, time to first relapse and DMT choice to understand influence of these factors on early clinical management decisions.Results176 people were diagnosed in Cardiff in the 2-year study period. 2 were excluded due to missing baseline imaging. At the time of diagnosis 60% had 3 or more APFs. A higher number of APFs was associ- ated with the decision to prescribe high- versus moderate-efficacy therapies (OR= 1.34; 95% CI 1.04, 1.73, p=0.02) and males were also more likely to receive high-efficacy DMTs (OR 2.11; 95% CI 1.32-3.36, p=0.002).ConclusionsThese data provide description of the frequency and patterns of APFs at time of MS diagnosis and illustrate their influence on initial therapeutic interventions and short-term outcomes.
Autonomic dysfunction after moderate-severe traumatic brain injury: symptom spectrum and clinical testing outcomes
Authors: Li Lucia , Vichayanrat Ekawat , Giovane Martina del , Lai Helen , Iodice Valeria 
Published: August 2022

BackgroundSurvivors of moderate-severe traumatic brain injury (msTBI) frequently experience trouble- some unexplained somatic symptoms, which may be attributable to autonomic dysfunction.MethodsWe conducted two cohort studies. Cohort 1 comprises msTBI patients (with controls) prospec- tively recruited from a regional referral TBI outpatient clinic, in whom we assessed subjective burden of autonomic symptoms using the Composite Autonomic Symptom Score (COMPASS31) questionnaire. Cohort 2 comprises msTBI patients who had clinical autonomic function testing, retrospectively identified from referrals to a national referral autonomics unit.ResultsCohort 1 comprises 39 msTBI patients (10F:20M, median age 40 years, range 19-76), with median time since injury 19 months (range 6-299), and 44 controls (22F:22M, median age 45, range 25-71). Patients had significantly higher mean scores than controls in the weighted total COMPASS-31 score (p<0.001), and also gastrointestinal, orthostatic and secretomotor subscores (corrected p<0.05). Total COMPASS31 score inversely correlated with subjective rating of general health (p<0.001, rs=-0.84). Cohort 2 comprises 18 msTBI patients (7F:11M, median age 44 years, range 21-64), with median time between injury and testing 57.5 months (range 2-416). Clinical autonomic function testing revealed a broad spectrum of autonomic dysfunction in 13/18 patients.DiscussionOur results provide evidence for clinically relevant autonomic dysfunction after msTBI, even at the chronic stage. We advocate for routine enquiry about potential autonomic symptoms, and demons- trate the utility of formal autonomic testing in providing diagnoses.
136 NOVA primary results randomised controlled study of natalizumab Q6W versus continued Q4W treatment for MS
Authors: Foley John , Defer Gilles , Ryerson Lana Zhovtis , Cohen Jeffrey , Arnold Douglas , Butzkueven Helmut , Cutter Gary , Giovannoni Gavin , Killestein Joep 
Published: August 2022

BackgroundNatalizumab every-6-week (Q6W) dosing is associated with lower progressive multifocal leukoencephalopathy risk than every-4-week dosing (Q4W) in retrospective analyses. NOVA is the first randomised trial to assess Q6W efficacy.ObjectiveEvaluate natalizumab Q6W efficacy in patients previously treated with natalizumab Q4W for≥12 months compared with continuation of Q4W over 72 weeks.MethodsNOVA is a randomised, controlled, open-label, rater-blinded phase 3b trial. Included patients were treated with natalizumab Q4W without relapse for ≥12 months. Patients were randomised 1:1 to Q4W (n=248) or Q6W (n=251). The primary endpoint was new/newly enlarging T2 (N/NET2) lesions. Secondary endpoints included clinical and safety outcomes.ResultsProportions of patients with N/NET2 lesions were low in both arms (Q4W:4.1%; Q6W:4.3%). Differ- ences in mean N/NET2 lesions for Q4W and Q6W (primary estimand: 0.05 vs 0.20 [P=0.0755]; secondary estimand: 0.06 vs 0.31 [P=0.0437]) were driven by two Q6W patients with extreme (≥25) values. Secondary outcomes were similar for Q4W and Q6W.ConclusionsOverall, NOVA data suggest most patients stable on natalizumab Q4W can switch to Q6W without clinically meaningful loss of efficacy. Support: Biogen. Disclosures on poster.
158 Natalizumab treatment satisfaction in TONiC-MS study: preliminary results from i.v.participants on infusion experience
Authors: James Bethan , Mills Roger , Vonsy Jean , Langdon Dawn , Ando Hikari , Young Carolyn 
Published: August 2022

BackgroundMS patients’ perceptions and treatment satisfaction with natalizumab-i.v., as well as their experiences if they switch from natalizumab i.v. to natalizumab-s.c., are being collected in a prospective, observational study, nested in the Trajectories of Outcome on Neurological Conditions (TONiC-MS) study.MethodsThese are postal questionnaire, interim results of participants’ experiences with natalizumab infusions; no patients had switched to s.c. yet.Results56 participants, treated at 19 hospitals, responded by 7 January 2022. Median duration of treatment was 7.66 years; 50% (28) had received natalizumab as their first disease modifying therapy. Infusions occurred monthly for 59% (33) and every 6 weeks for 35.7% (20). Infusions normally took 1-2 hours (89.3%) and 52% (29) reported no post-treatment observation.42.6% (23/54) normally required ≥2 attempts at cannula insertion, of whom 34.8% (8/23) had experienced an infusion treatment which required more than 5 attempts. Pain at cannula site was experienced by 14.3% (8/56). Worry about successful cannulation was reported by 25% (14/56).DiscussionThis is the first UK real-world study on natalizumab patients’ perceptions. These preliminary results highlight cannulation challenges experienced by some i.v. patients. As some patients switch to s.c., we will assess differences and patient preference between the two formulations.
159 The growing role of the neuropharmacist: helping to deal with staff shortages in other professions
Authors: Mathews Joela , Dorsey-Campbell Rachel 
Published: August 2022

IntroductionThis audit of existing neuropharmacists shows how the role has grown over the years to help look after tasks suited to their skill set such as governance, introduction of new medication and path-way design, which has helped neurology teams in utilising the skills of each member of the team appropriately.AimTo showcase the growing role of the neuropharmacist.MethodsA survey of existing neuropharmacists about their current roles and duties was undertaken, utilising the network of 50 neuropharmacists across the UK.ResultsThe role of the neuropharmacist has grown with subspecialism occurring in areas such as MS, headache, epilepsy and parkinsons disease. Patient facing clinics, leading on governance for the neu- roscience team, introduction of new medication to pathways and taking part in research across the healthcare economy (ie with primary care) are all areas that the neuropharmacist has been involved.ConclusionsThe role of the neuropharmacist is diverse and can be utilised by the neurology team to ensure appropriate skill set are used to deliver the best care to patients. It is hope this work will help teams that do not have a neuropharmacist to develop business cases and redesign patient and disease pathways to include other members of the team.
161 Recurrent painful ophthalmoplegic neuropathy vs oculomotor schwannoma
Authors: Seddigh Arshia , Jacob Saiju 
Published: August 2022

A 23-year-old female was admitted to ED two weeks after delivery with severe migrainous headaches and a painful pupil-sparing partial right third nerve palsy presenting as diplopia on upward and lateral gaze and a partial ptosis. This was the third such presentation for her as she was diagnosed with oph- thalmoplegic migraine (OM) since 8 years old. A second episode at the 18 years of age required steroid treatment due to a delayed recovery for few months.Repeat orbit MRI confirmed slightly grown lesion on the right oculomotor nerve compared scans 4 years apart appearing as a thickened nodular enhancement between the P1 segment and superior cerebel- lar artery. Multiple neuro-oncology and neuro-radiology MDTs confirmed this lesion to be an oculomotor nerve schwannoma. She had to be treated with steroids due to deficits and 2 months later while migrain- ous headache was fully resolved, she was still left with subtle upward and lateral gaze diplopia. She will have surveillance imaging and follow up.Recurrent Painful Ophthalmoplegic Neuropathy (RPON) is replacing OM and expected to be associated with a resolution of the enhancement. Schwannomas on the other hand are known to be growing during pregnancy and affected by hormonal changes. Transient or recurrent oculomotor nerve deficits may be the primary manifestations of cranial nerve schwannoma and we hypothesise this tumour being the cause of her RPON which must be considered in OM.
168 Traumatic brain injury and sociodemographic factors: a review
Authors: Vidot Micha , Wu Kit , Mitchell James , Nitkunan Arani , Carr Georgina 
Published: August 2022

BackgroundTo improve equity of service, in line with the aspirations of public policy across the UK, it is imperative that we understand how sociodemographic factors affect the management and care of traumatic brain injury (TBI).AimsTo describe the relationship between sociodemographic factors and the epidemiology, clinical factors, diagnosis, treatment, patient experience and outcomes for people with TBI.MethodsWe conducted a focused review of published literature from 2000 to 2021 discussing TBI and each of the patient protected characteristics, as outlined in the Equality Act 2010, with additional factors such as education, employment and socioeconomic status also included.ResultsThere is some evidence investigating TBI in regards to age, race, sex and gender. There are gaps in research exploring the relationship between TBI and disability, gender reassignment, marriage and civil partnership, pregnancy, religion, sexual orientation, geographical variation, socioeconomic status, settlement status, education and employment.DiscussionWhilst there is some data on the incidence of TBI, further research is required to examine the association of certain sociodemographic protected characteristics to aid improvements in patient experience and outcomes.
173 Transcriptional phenotypes of a human stem cell model of Spinal Bulbar Muscular Atrophy (SBMA)
Authors: Devine Helen , Malik Bilal , Tyzack Giulia , Hanna Michael , Greensmith Linda , Patani Rickie 
Published: August 2022

BackgroundSpinal bulbar muscular atrophy is a slowly progressive neurodegenerative disease which affects lower motor neurons (MNs). It is caused by a trinucleotide polyglutamine (CAG) repeat expansion in the androgen receptor (AR) gene but the precise mechanisms of degeneration of the MNs in SBMA are complex and remain poorly understood. There are currently no available treatments for patients.ObjectivesThe aim of this study was to develop a human iPSC model of SBMA patient MNs in order to characterise early transcriptomic events in SBMA.MethodsHuman iPSCs were differentiated into spinal MNs using an established, developmentally-rational- ised protocol. Samples were collected at key stages in motor neurogenesis for RNA-sequencing followed by transcriptomic and splicing analysis. Live-cell imaging assays for mitochondrial membrane potential and axonal transport of mitochondria and signal endosomes were performed to validate transcriptomic findings.ResultsOver-representation analysis of differentially expressed genes revealed enrichment of DNA damage response and cell cycle pathways. There were reduced transcripts of genes involved in mito- chondrial pathways with reduced mitochondrial membrane potential and anterograde mitochondrial transport in SBMA on live-cell imaging. Alternative splicing events were common and involved adherens junction and extracellular matrix pathways.ConclusionEarly transcriptional dysregulation, alternative splicing and mitochondrial dysfunction were seen in SBMA MNs as well as genes linked to defective p53/DNA damage response and the cell cycle.These cellular phenotypes offer potential targets for future clinical treatments.
Prevention of neurological complications during COVID-19: a retrospective analysis of the ISARIC4C national cohort
Authors: Grundmann Alexander , Hardwick Marc , Wu Chieh-Hsi , Semple Malcolm , Böhning Dankmar , Pett Sarah , Michael Benedict , Thomas Rhys , Galea Ian 
Published: August 2022

Neurological complications occur in 4% of patients following acute COVID-19 infection, causing significant morbidity with lasting health economic consequences. However treatment studies to date in COVID-19 have not addressed neurological complications as outcome measures.We therefore performed a retrospective, non-interventional cohort study using the ISARIC-4C platform, assessing 62,729 hospital inpatients with severe COVID-19 between 31 Jan 2020 and 29 Jun 2021. Treatment with dexamethasone, remdesivir or both was compared to standard of care. The primary outcome was a neurological complication, namely stroke, seizure, meningitis/encephalitis or any other neurological complication, occurring at the point of death, discharge, or resolution of the COVID-19 clinical episode. A propensity scoring methodology was used to balance confounding between treatment groups and between patients with and without neurological complications.Treatment with dexamethasone, remdesivir or both reduced the incidence of neurological complications from severe COVID-19, with odds ratios of 0.76 (0.69-0.83), 0.68 (0.51-0.90) and 0.64 (0.56 -0.72) respec- tively. Neurological complications were associated with increased length of hospital stay, worse ability to self-care on discharge and increased mortality.This study is the first to focus on the prevention of neurological complications and strongly supports the continued use of both dexamethasone and remdesivir in severe COVID-19. Our results suggest that the established benefit of dexamethasone on mortality in COVID-19 is not associated with an increased burden of long-term neurological disability.
178 Motor neurone disease and sociodemographic factors: a review
Authors: Vidot Micha , Wu Kit , Mitchell James , Nitkunan Arani , Carr Georgina 
Published: August 2022

BackgroundTo improve equity of service, in line with the aspirations of public policy across the UK, it is imperative that we understand how sociodemographic factors affect the management and care of patients with motor neurone disease (MND).AimsTo describe the relationship between sociodemographic factors and the epidemiology, clinical factors, diagnosis, treatment, patient experience and outcomes for people with MND.MethodsWe conducted a focused review of published literature from 2000 to 2021 looking into MND and each of the patient protected characteristics, as outlined in the Equality Act 2010, with additional factors such as education, socioeconomic status and employment also included.ResultsThere is plenty of published literature exploring amyotrophic lateral sclerosis (ALS) and the rela- tionship with age, race, sex and gender.Minimal published data could be found for disability, gender reassignment, marriage and civil partner- ship, pregnancy and maternity, religion and beliefs, sexual orientation, socioeconomic status, settlement status, education and employment. Additionally, there was a lack of data looking into this for the different types of MND.DiscussionResearch in MND has focused heavily upon ALS. Further research into all patient protected characteristics and the different types of MND is required to improve equity in care and patient outcomes.
187 SUNFISH Part 2: 24-month efficacy of risdiplam compared with external control comparators
Authors: Servais Laurent , Day John W , Mazzone Elena S , Oskoui Maryam , Baranello Giovanni , Gerber Marianne , Martin Carmen , McIver Tammy , Yeung Wai Yin , Mercuri Eugenio 
Published: August 2022

Risdiplam (EVRYSDI®) is an oral survival of motor neuron 2 (SMN2) premRNA splicing modifier approved by the EMA and MHRA for the treatment of patients aged ≥2 months, with a clinical diagnosis of Type 1, 2 or 3 spinal muscular atrophy (SMA) or 1–4 copies of SMN2.SUNFISH (NCT02908685) is a two-part, randomised, placebo-controlled, double-blind study in a broad population of patients aged 2–25 years at enrolment, with Type 2/3 SMA. Part 2 assesses the efficacy and safety of the Part 1-selected dose of risdiplam versus placebo in Type 2 and nonambulant Type 3 SMA. Participants were treated with risdiplam or placebo for 12 months; all participants then received risdiplam until Month 24, when patients were offered the opportunity to enter the open-label extension.The primary outcome of Part 2 – change from baseline to Month 12 in the 32-item Motor Function Measure total score in patients treated with risdiplam (n=120) versus placebo (n=60) – was met. Here we present analyses to compare 24-month data from the risdiplam arm with an external comparator dataset con- taining data from participants in the NatHis-SMA study (NCT02391831) and the placebo arm of a Phase 2 study of olesoxime in patients with SMA (NCT01302600).
Epilepsy mortality in Wales during COVID-19
Authors: Daniels Helen , Lacey Arron S , Mikadze David , Akbari Ashley , Fonferko-Shadrach Beata , Jolling-Hurst Joe , Rees Mark I , Powell Robert H , Kerr Michael P , Pickrell William Owen 
Published: August 2022

PurposeWe aimed to compare mortality rates in people with epilepsy in Wales during the pandemic with pre-pandemic rates.MethodsWe performed a retrospective study using population-scale anonymised health records. We identified deaths in people with epilepsy (DPWE), those with a diagnosis of epilepsy, and deaths associ- ated with epilepsy (DAE), where epilepsy was recorded as a cause of death. We compared death rates in 2020 with average rates in 2015–2019 using Poisson models.ResultsThere were 188 DAE and 628 DPWE in Wales in 2020 (death rates: 7.7/100,000/year and 25.7/100,000/year). The average rates for DAE and DPWE from 2015 to 2019 were 5.8/100,000/year and 23.8/100,000/year, respectively. Death rate ratios (2020 compared to 2015–2019) for DAE were 1.34 (95%CI 1.14–1.57, p<0.001) and for DPWE were 1.08 (0.99–1.17, p = 0.09). The death rate ratios for non-COVID deaths (deaths without COVID mentioned on death certificates) for DAE were 1.17 (0.99–1.39, p = 0.06) and for DPWE were 0.96 (0.87–1.05, p = 0.37).ConclusionsThe significant increase in DAE in Wales during 2020 could be explained by the direct effect of COVID-19 infection. Non-COVID-19 deaths have not increased significantly but further work is needed to assess the longer-term impact.
199 Mechanical thrombectomy for acute ischaemic stroke – outcomes from Sheffield
Authors: Moore Sophie , Dyde Richard , Tse George , Nagaraja Sanjoy , Endean Keith , Redgrave Jessica , Lindert Ralf , Harkness Kirsty 
Published: August 2022

IntroductionMechanical thrombectomy is now in routine use for acute ischaemic stroke. This service audit examines outcomes and complications in the Sheffield regional centre.MethodsData was collected retrospectively for all patients undergoing mechanical thrombectomy at Sheffield Teaching Hospitals from March 2020 – February 2021 using case notes and digital records. The data was analysed for the whole group (n=33), and for the subgroup of patients (n=8) aged over 80.Results33 patients, aged 31-87, underwent mechanical thrombectomy. 88% had successful revasculari- sation (TICI grade 2b/3). 48% had a good functional recovery (modified Rankin scale 0-2).6 patients had haemorrhagic transformation, though none met the SITSMOST criteria for symptomatic intracerebral haemorrhage secondary to procedure. 6 patients (18%) did not survive to 90 days.In the group aged over 80, outcomes were significantly worse. In this group the rate of successful revas- cularisation was 63%, and good functional recovery (mRS 0-2) was 13%. 90 day mortality was 38%.ConclusionsOutcomes from mechanical thrombectomy at Sheffield teaching hospitals are good, with nearly half of patients having a good functional recovery. However, outcomes in the subgroup of patients aged over 80 were significantly poorer, with high complication and mortality rates; this warrants further study.
204 Improving access to cardiac monitoring for acute stroke patients: a quality improvement project
Authors: Scott Nicholas , Curbera Nicolas , McManus Julie 
Published: August 2022

IntroductionAtrial fibrillation (AF) is an important modifiable risk factor for ischaemic stroke. Detection of AF following acute stroke presentations can be achieved with early prolonged cardiac monitoring.MethodsWe sought to review access to cardiac monitoring (multi-day ambulatory ECG) for stroke patients at the Royal Alexandra Hospital (RAH), Paisley, UK. We retrospectively reviewed patients admitted to the acute stroke unit at the RAH over 3 months (phase I) and then subsequently (phase II) in the 3 months following the implementation of ‘in-house’ cardiac monitors.ResultsA total of 121 patients were reviewed in phase I and 142 patients in phase II. In phase I, 70 patients had cardiac monitors requested out of which 45 had been done (64.3%). In phase II, 81 cardiac monitors had been requested and 71 (87.7%) had be carried out. Average time from request to cardiac monitor- ing being performed was reduced from 17 days in phase I to 5 days in phase II.AF detection as a percentage of cardiac monitors carried out was similar between the two phases increasing slightly from 15.6% to 16.9%.ConclusionThe establishment of ‘in-house’ cardiac monitoring improves access to early cardiac moni- toring for patients.
Clinical relevance and utility of GAD65 antibodies in neurological disease: an eight year cohort study
Authors: Brown Rachel , Thomas-Black Gilbert , Garcia-Moreno Hector , Chapman Miles , Chou Michael , Hart Melanie , Fleszar Zofia , Zandi Michael , Giunti Paola , Lunn Michael P 
Published: August 2022

Neurological syndromes associated with glutamic acid decarboxylase (GAD) antibodies provide a challenge in understanding disease pathogenesis, interpreting antibody results, and deciding manage- ment. We retrospectively reviewed 277 patients with positive anti-GAD antibodies (≥ 10 IU/mL) at our centre between 2012-2020. 154 (56%) had one or more neurological disorders including 27 stiff person spectrum disorders (SPSD) (18%), 20 cerebellar ataxia (13%), 18 epilepsy (12%), 18 encephalitis (12%),12 ‘mixed’ (8%), and 59 other neurological disorders (38%). Co-existing autoimmunity was common; 57 (33%) had diabetes and 46 autoimmune thyroid disease (30%). A wide range of GAD titres was seen, but serum GAD antibody titres were significantly higher in patients with ‘classical’ GAD antibody syndromes than other neurological disorders (p<0.0001) or diabetes only (p<0.0001). In patients with ‘classical’ GAD antibody syndromes, both specific neurological syndrome and the presence of diabetes influenced serum antibody titres; neurological syndrome also affected CSF titres. Patients with SPSD or encephalitis were most likely to receive immunotherapy and the most likely to respond to treatment. Overall, GAD antibody titres were not associated with response to treatment. This is largest GAD-antibody cohort reported and together these data provide key lessons for understanding and interpreting GAD antibody-associated syndromes in clinical practice.