bluuebunny/crossref_metadata_2025_split huggingface dataset:
105 A rare presentation of Bickerstaff’s brainstem encephalitis
Authors: Terry Robyn , Wislocka-Kryjak Magdalena 
Published: August 2022

Bickerstaff’s Brainstem Encephalitis (BBE) is a condition causing impairment of sensorium in association with ophthalmoplegia and ataxia. Here we present a case of BBE presenting with bilateral vocal cord paralysis.A 35-year-old female presented with a sore throat and shortness of breath in the context of a fall and ankle injury the previous day. She became confused and agitated in hospital. Several hours after pres- entation she was found cyanosed with stridulous breathing (with normal saturations). Fibre-optic nasola- ryngoscopy revealed bilateral vocal cord palsy. She was intubated and transferred to ICU. Investigations including a full infection screen, CSF analysis and MRI were normal and non-diagnostic. Examination during a sedation hold revealed a unilateral third, fourth, and bilateral sixth and seventh cranial nerve palsies. She had flaccid quadriparesis and was globally areflexic. Nerve conduction studies showed a motor predominant polyneuropathy. A diagnosis of BBE was made based on the clinical findings with acute confusion. She was treated with plasma exchange and immunoglobulins and was discharged with almost complete recovery.There are no previous case reports of vocal cord paralysis being the presenting feature of BBE. Neurologi- cal disease accounts for only 12% of cases of bilateral cord palsy. These causes may be systemic such as myasthenia gravis or diphtheria, or focal affecting the nucleus ambiguus in the medulla. However, clini- cians must recognise these cases promptly to ensure adequate investigation and treatment.
112 Parkinson’s disease and sociodemographic factors: a review
Authors: Wu Kit , Vidot Micha , Mitchell James W , Nitkunan Arani , Carr Georgina 
Published: August 2022

BackgroundUnwarranted variation in treatment, care and support for people with Parkinson’s Disease (PD) is well documented. To improve equity of service, in line with the NHS Long Term Plan, it is imperative that we understand how sociodemographic factors affect management and care of PD.AimTo review published literature between sociodemographic factors and clinical factors, diagnosis, treatment and outcomes for people with PD.MethodWe conducted a focused review of published literature between 2000-2021 to outline the evidence describing the relationship between the ten protected characteristics of the Equality Act 2010 and clinical factors, treatment and outcomes in PD. Other factors such as deprivation, settlement status, education and employment were also explored.ResultsThere is an abundance of published literature on age, disability, sex and gender over the twenty- year period. Studies on race and education and employment yielded mixed results. Evidence is lacking for gender reassignment, marriage and civil partnership, pregnancy and maternity, religion and belief, sexual orientation, deprivation, geographical variation (within UK), immigration and settlement.DiscussionPD impacts on many facets of life. This review has identified many gaps in knowledge of the effect of sociodemographic factors affecting PD. More research is needed to better provide a more equitable service to patients.
125 Real world data evaluating efficacy and safety of oral cladribine for multiple sclerosis
Authors: Nasir Moneeb , Rabvukwa Plaxedes , Fuller Sarah , Chaudhuri Abhijit , Mattoscio Miriam 
Published: August 2022

BackgroundOral cladribine has been effective in clinical trials but only a few studies report real world data. This study assessed efficacy and safety of oral cladribine in an east London hospital.MethodsData were retrospectively collected on clinical relapses, new MRI lesions, EDSS change, annu- alised relapse rates (ARR), lymphocyte counts, and infections.Results56 patients had cladribine in our study (33 had cladribine years 1+2; 23 had only year 1; mean follow-up 24.9 months). Of 56 patients: 3 (5.4%) had a clinical relapse, 7 (12.5%) developed new asymp- tomatic MRI lesions, and 12 (21.4%) had EDSS progression. Overall, ongoing disease activity (either clinical relapse, MRI activity or EDSS progression) was seen in 15/56 patients (26.8%). EDSS improvement was seen in 12 patients (21.4%). Multiple logistic regression showed that prior ARR (p=0.18), baseline EDSS (p=0.52) and gender (p=0.49) did not influence likelihood of ongoing disease activity. Lymphopenia was seen in 31/56 patients (grade 3 = 6; grade 4 = 0).ConclusionsFewer patients had relapses in our study as compared to other similar studies. This may be due to the lower median baseline EDSS (3.5) and shorter follow-up in our cohort. The proportion of patients with EDSS progression, however, was similar to other studies.
147 Siponimod preserves retinal thickness: findings from the EXPAND OCT substudy
Authors: Vermesch Patrick , Gold Ralf , Bar-Or Amit , Cree Bruce , Fox Robert , Giovannoni Gavin , Li Bingbing , Piani-Meier Daniela , Karlsson Goeril , Kappos Ludwig 
Published: August 2022

AimTo evaluate changes in retinal thickness (µm), including the retinal nerve fibre layer (RNFL) and combined ganglion cell and inner plexiform layers (GCIPL), in patients receiving siponimod or placebo.MethodsChanges in optical coherence tomography (OCT) measurements from screening to M12 and M24 were compared between the two treatment groups using mixed models for repeated measures adjusted for treatment, age, sex and respective baseline OCT variables.ResultsThe OCT sub-study included 159 patients (siponimod, n=104; placebo, n=55). RNFL thickness at M12 numerically favoured siponimod (0.39 vs −0.99; p=0.099) but not at M24 (−0.05 vs. 0.48; p=0.642). However, fewer assessments were available for RNFL at M24 than M12. The between-group difference in GCIPL thinning was 0.21 (−2.55 vs −2.76; p=0.875) at M12 and 3.82 (−0.47 vs −4.29; p=0.01) at M24. Siponimod reduced retinal thinning vs placebo at M12 (change from baseline: 0.66 vs −1.86; p=0.006) and M24 (−0.05 vs −2.3; p=0.033). Changes of retinal thickness and GCIPL at the subfield areas also favoured siponimod over placebo.ConclusionsThese results support the sensitivity of OCT as a measure of tissue damage in progressive MS and are in line with previously reported beneficial effects of siponimod on other neurodegeneration related outcomes. Funding: Novartis Pharma AG, Basel, Switzerland.
148 Treating newly diagnosed relapsing-remitting multiple sclerosis (RRMS): a 2021 clinician survey in the United Kingdom
Authors: Evangelou Nikos , Mattoscio Miriam , Coutts Mhairi , Andiappan Mano , Sawtell Teresa , Rhys Katherine 
Published: August 2022

BackgroundAs new treatment approaches become available for RRMS it is important to understand clinical treatment decision-making.MethodsWe used a structured questionnaire to interview UK healthcare professionals (HCPs) about their clinical treatment approaches for RRMS.ResultsOf 38 HCPs interviewed, 53% were multiple sclerosis (MS) Consultants, 34% MS specialist nurses, 11% neurologists with an MS interest (3% other). The most important treatment goals for newly diagnosed RRMS were modifying/reducing relapse, delaying progression to disability and maintaining quality of life, reported by 63% (24/38), 58% (22/38) and 50% (19/38) of respondents, respectively. 74% of respond- ents strongly agreed and 24% agreed early treatment is essential for better outcomes in most patients. The (mean [SD]; n=37) estimated percentage of patients treated with high efficacy early or escalation approaches were 42.1% (21.8) and 58.3% (20.8), respectively; 66% of respondents agreed these proportions reflected the treatment approach they would like to take. For those disagreeing (34%), the mean (SD) reported percentage of patients they would ideally treat with high efficacy and escalation approaches were 66.2% (18.0) and 33.8% (18.0), respectively.ConclusionsWhilst the majority of HCPs agreed that early treatment of RRMS is essential, there was vari- ability in reported and ideal treatment approaches.
149 Down but not out repurposing depression treatments for multiple sclerosis with the UK MS register
Authors: Rodgers Jeff , Middleton Rod , Witts James , Craig Elaine , Tuite-Dalton Katie , Nicholas Richard ,   MS Register Research Group
Published: August 2022

IntroductionRepurposing treatments in multiple sclerosis (MS) has resulted in several candidates that are currently in phase 2 and 3 trials but to test candidate therapies requires a prolonged and costly study. Real world data offers the opportunity to assess in non-randomised data the potential of a range of commonly used therapies. The UK MS register is a UK-wide real-world dataset of 20,000 subjects where regular MS outcomes are collected. Using this dataset, we have recently shown the benefits of disease modifying therapies, and smoking cessation in MS. We aimed to determine if such a resource could be used to determine to utility of potential repurposed drug candidatesMethodsOf 20,000 subjects in the UK MS register we identified those on any antidepressants treatment who had at least 2 follow up visits from baseline after starting treatment. We then identified those who had completed the Hospital Anxiety and Depression Scale (HADS) and the Multiple Sclerosis Impact Scale (MSIS-29) scales in addition at each visit.Results3559 subjects on 4294 unique antidepressant treatments were identified (SSRIs: 1852, Tricyclics: 1893, SNRIs: 365. NaSSa: 164, and SARIs: 20). 533 had a baseline visit and 2 follow-up visits with HADS and MSIS-29 questionnaires, where baseline was the beginning of treatment.ConclusionsThe UK MS Register cohort of pwMS can be utilised to support real-world initiatives to inves- tigate potential repurposed candidates.
151 Updated analysis of pregnancy outcomes for patients with MS in a dimethyl fumarate exposure registry
Authors: Rog David , Hellwig Kerstin , McGuigan Christopher , Mokliatchouk Oksana , Branco Filipe , Lyons Jennifer , Everage Nicholas 
Published: August 2022

IntroductionDimethyl fumarate (DMF) is not recommended during pregnancy and should only be used if the potential benefit justifies potential foetal risk. Given limited pregnancy data, the UK and Ireland have enrolled DMF-exposed pregnant women in an ongoing international registry assessing pregnancy outcomes. In the general population, 62% of pregnancies end in live birth, 22% in abortion, and 16% in foetal loss, with similar rates in multiple sclerosis (MS) patients.MethodsWomen with MS exposed to DMF since the first day of their last menstrual period before con- ception/during pregnancy were included. UK/Ireland Coordinating Centres liaised directly with patients and healthcare providers.ResultsAs of March 2021, 403 patients (19 UK/Ireland) were enrolled. Of 350 reported pregnancy outcomes (19 UK/Ireland), 329 (94%) represented live births (100% UK/Ireland). Of 326 infants with known gestational age,298 births (91%) were full-term (100% UK/Ireland) and 28 (9%) premature (<37 weeks). Of the 21 (6%) cases of foetal loss, 19 were spontaneous abortions (1 each ectopic and molar pregnancy) and 2 foetal deaths (>28 weeks). There was one neonatal death. Nine infants (2 UK/Ireland) had EUROCAT-confirmed birth defects.ConclusionsThe observations are consistent with MS and general populations.SupportBiogen. Disclosures on poster.
153 ChariotMS – cladribine to halt deterioration in people with advanced multiple sclerosis (pwAMS)
Authors: Schmierer Klaus , Baker David , Nawaz Tanjil , Allen-Philbey Kimberley , Barkhof Frederik , Chataway Jeremy , Hooper Richard , Mihaylova Borislava , Hobart Jeremy , Pavitt Sue 
Published: August 2022

BackgroundDisease-modifying treatments (DMT) have transformed the management of people with MS. However, those with an EDSS>6.5 (pwAMS) are considered not suitable for DMT due to (i) a focus on ambulation as outcome measure, (ii) the assumption that in pwAMS, inflammation plays no role, and (iii) a disregard for potentially length-dependent neuro-axonal damage. Cladribine tablets (Mavenclad®) is an effective, convenient, relatively safe DMT licensed for people with highly-active relapsing MS. Cladrib- ine depletes B (less so T) cell subsets, particularly memory B cells, putatively key for disease control in MS.AimsTo test efficacy, safety and cost-effectiveness of cladribine tablets in pwAMS (EDSS 6.5-8.5), expand mechanistic understanding of cladribine and provide evidence for NHS adoption.MethodsRandomised, double-blind, placebo-controlled phase IIb trial. Primary outcome measure, 9-hole peg test speed at 104 weeks vs baseline. Sample size calculations indicated n=200 required to detect 15% treatment effect in 9HPT peg-speed with 90% power at 5% significance and 20% drop-out.ResultsNine/20 trial sites currently open for recruitment. Five participants already enrolled. Full recruit- ment predicted in Q1/2023.ConclusionsChariotMS is the first DMT-trial focussing on pwAMS. If successful, ChariotMS could expand the DMT landscape to include pwAMS, and provide a platform for add-on therapies.
154 Incidence of persistent lymphopenia in people with multiple sclerosis on dimethyl fumarate
Authors: Wood Callum , Pickersgill Trevor , Willis Mark , Robertson Neil , Tallantyre Emma 
Published: August 2022

BackgroundDimethyl fumarate (DMF) is a disease modifying therapy (DMT) used to manage Multiple Sclerosis (MS). The recently revised Summary of Product Characteristics (SPC) recommends increased monitoring or cessation of this medication for persistent (> 6 months) lymphopenia, because of an increased risk of Progressive Multifocal Leukoencephalopathy. Awareness of the frequency of persistent lymphopenia will guide clinical decisions regarding drug choice and safety monitoring.MethodsMedical records of 146 patients with MS, started on DMF between 2014-2020 who received > 6 months of treatment were reviewed to identify the incidence, duration, and risk factors of persistent lymphopenia.ResultsOverall, 16 (11%) people with MS taking DMF experienced persistent moderate lymphopenia (0.5-0.7x109/L for > 6m) and 5 (3%) experienced persistent severe lymphopenia (<0.5 x 109/L for > 6m). Mean times to persistent moderate and severe lymphopenia were 10.6 months and 25.5 months respec- tively. Increased age was a predictor for persistent lymphopenia (B=0.071, p=0.004); sex and previous DMT were not.ConclusionPersistent moderate – severe lymphopenia is relatively common in people on DMF. More robust guidelines for both risk/benefit of continuing DMF despite persistent lymphopenia, and DMT sequencing following DMF in people with lymphopenia are required.
155 Reasons for stopping MS disease modifying treatment in a UK cohort
Authors: John Freddie St , Froud Joseph , Willis Mark , Anderson Valerie , Uzochukwu Emeka , Wynford-Thomas Ray , Tallantyre Emma , Robertson Neil ,   et al,   on behalf of UK MS Registries Consortium
Published: August 2022

BackgroundSuccess of disease modifying therapy (DMT) for relapsing MS (RMS) is dependent on both effectiveness and adherence. We have explored reasons for stopping DMT in a large multicentre RMS cohort to inform disease management.MethodsData was collected from sequential RMS patients receiving a DMT in 8 UK MS centres. DMT discontinuation events were recorded according to a standardised classification comprising: adverse event, increased risk of adverse event, lack of efficacy, onset of progressive disease, patient choice, pregnancy/pre-conceptual care, other, unknown.ResultsData from 6,816 prescriptions in 4,102 patients (female 72%, mean 1.7 prescriptions, range 1-6 per patient) were analysed. The most common reason for stopping was lack of efficacy (37%) followed by adverse event (31%), increased risk of adverse event (10%) and then pregnancy/preconceptual care (9%). Reasons for stopping varied by treatment duration, age, sex and DMT. DMT discontinuation due to adverse events fell from 51% in year 1, to 15% in years 5-10; discontinuation due to lack of efficacy rose from 22% to 45%. Increasing disability was rarely a reason to stop DMT.ConclusionsThese data provide valuable insights into the real-world utility of MS DMTs and could provide a rationale to refine existing treatment pathways.
Acute inflammatory CNS diseases following vaccination against SARS-CoV-2
Authors: Francis Anna , Camera Valentina , Elhadd Kariem , Craner Matthew , Attfield Katherine , Iversen Astrid , Huda Saif , Fugger Lars , Palace Jacqueline 
Published: August 2022

BackgroundVaccination is a recognised trigger of ADEM and approximately 50% paediatric cases have antibodies to MOG. The SARS-CoV-2 mass vaccination programme could therefore trigger cases of MOGAD. Neuromyelitis optica (NMO) is an autoimmune inflammatory condition of the CNS associ- ated with antibodies to AQP4.MethodTen patients (ages 22 – 65 years) with antibodies to MOG or AQP4 were referred to the NHS England NMO service having developed acute onset CNS inflammation within 8 weeks of vaccination.ResultsEight patients had MOGAD, seven of whom received the AstraZeneca vaccine (AZV) and one the Pfizer vaccine (PV). Only the post-PV MOGAD patient presented with typical adult-onset phenotype of isolated ON. All post-AZV MOGAD patients presented atypically; 85.7% had LETM and 71.4% had intrac- erebral lesions, resembling ADEM more commonly seen in paediatric MOGAD. The atypical presentation supports a causative role of AZV, but the role of PV is less convincing.Two patients had AQP4-NMOSD with typical demographic features. Both received AZV. Less typically, one young adult presented with LETM rather than characteristic young adult ON, the other had a silent short segment myelitis, which is rarely seen in AQP4-NMOSD. Both patients achieved good outcomes.ConclusionWe discuss the potential causation and pathophysiological mechanisms.
167 mTBI Predict: a prospective biomarker study to predict outcomes in mild traumatic brain injury
Authors: Lyons Hannah , Belli Tony , Blanch Richard , Hampshire Adam , Jensen Ole , Mitchell James , Rogers Jack , Seemungal Barry , Withnall Rich , Sinclair Alexandra ,   et al
Published: August 2022

BackgroundMild traumatic brain injury (mTBI) is common accounting for 1.4 million hospital visits annually in the UK. Although classified as mild it leads to disproportionate impact on future health. Many suffer long-term disability driven by post-traumatic headache, mood and visual disturbances, vestibular dys- function, post-traumatic stress disorder, cognitive impairment and inability to work. Biomarkers to predict these outcomes are an unmet need.MethodsWe will conduct a longitudinal, prospective cohort study over 8 years, recruiting 800 participants (military, civilian and sports injuries) with an acute diagnosis of mTBI. At onset, assessment of biomarkers will include brain imaging, cerebral physiology, blood and saliva, headache, mental health, vision, balance, and cognitive performance. We will evaluate the ability of biomarkers to predict long-term complications at 6, 12 and 24 months (and at 10 years plus though NHS digital data).DiscussionThis UK mTBI consortium aims to identify accurate, reproducible and clinically practical mul- timodal biomarkers in mTBI. Biomarkers would identify those with a good prognosis who could rapidly return to activity and those likely to suffer complications focussing prompt and targeted therapy. This programme of research aims to deliver a step change in patient care and bring much needed advances in mTBI management.
180 NeuroHealth designing a well-being app for people with neuroscience conditions using co-production principles
Authors: King Rachel , Wu Kit , Symeon Chris , Wellington Sharon , Larcombe Karen , Dilley Mike 
Published: August 2022

IntroductionThe Neurological Alliance Patient Experience Survey 2019/2020 has highlighted the delay to access of neurological care, infrequent monitoring by specialists and a wide regional variation in referral to support services for chronic disease management in patients with neurological diagnosis.AimTo design a patient-held wellbeing app to support longitudinal symptom monitoring and provide signposting of support services for patients.MethodsThe project is led by the South London Neurosciences network, co-designed with its patient advisory group, King’s Health Partners and a medical technology firm (BMI Inc). Together, we identified key attributes which were beneficial to symptom monitoring. The app went through four cycles of devel- opment, and has been launched for public use.ResultsThe NeuroHealth app consists of 4 key sections: mood, sleep, diet and exercise, identified by the patient group as beneficial for daily symptom monitoring. Each section uses illustrations and can be customised to individual needs. Such longitudinal recordings can be shared with health professionals and may help improve joint decision-making.SummaryNeuroHealth app is a co-designed and freely available digital resource which can benefit chronic condition monitoring and self-management.
186 Risdiplam through the UK early access to medicines scheme for patients with spinal muscular atrophy
Authors: Scoto Mariacristina , Galtrey Clare , Hewamadduma Channa , Keane Paul , Lilleker James B , Marini-Bettolo Chiara , Phillips Zoe , Sharp Becky , Wenham Andrew , Baranello Giovanni 
Published: August 2022

BackgroundRisdiplam is the first oral spinal muscular atrophy (SMA) treatment and was made available in the UK through an Early Access to Medicines Scheme (EAMS), which enrolled patients between September 2020–July 2021.MethodsRisdiplam’s EAMS indication was for patients with Type 1/2 SMA, ≥2 months old and not suitable for authorised SMA treatments. Patient characteristics and risdiplam-provision data from treating physi- cians, and patient/caregiver feedback, were collected.ResultsOf 242 patients enrolled, 92 were children (<18 years, 38.0%) and 150 were adults (62.0%). Most had Type 2 SMA (90.1%; Type 1: 9.9%). Most commonly reported comorbidities and clinical management characteristics were scoliosis (99/242; 40.9%), previous spinal surgery (82/242; 33.9%) and ventilatory support (79/242; 32.6%). Risdiplam was the first disease-modifying SMA therapy that most patients had received (155/242; 64.0%), including 7 (aged 15–33) with the more severe Type 1 form. Most patients who received risdiplam did so through sponsor-funded home delivery vs. hospital pharmacy collection (226/234; 96.6% vs. 6/234; 2.6% [not reported: 2/234]).ConclusionsRisdiplam was made available to a varied SMA population through the EAMS, targeting patients otherwise unable to access disease-modifying treatment. Many patients received disease- modifying treatment for the first time, addressing a significant unmet need.