bluuebunny/crossref_metadata_2025_split huggingface dataset:
178 Long-term efficacy of ocrelizumab in relapsing multiple sclerosis
Authors: Giovannoni Gavin , Hauser Stephen L , Brochet Bruno , Montalban Xavier , Naismith Robert T , Wolinsky Jerry S , Hubeaux Stanislas , Mehta Lahar , Model Fabian , Kappos Ludwig 
Published: March 2023

BackgroundThe efficacy and safety of ocrelizumab in relapsing multiple sclerosis were demonstrated in the double-blind control period of the Phase III OPERA I/II trials (NCT01247324/NCT01412333). Here we assessed the efficacy of switching to or maintaining ocrelizumab therapy after 3 years’ follow-up in the open-label extensions (OLEs) of these studies.MethodsAt OLE commencement, patients continued ocrelizumab (OCR-OCR) or switched from interferon-β-1a (IFN) to ocrelizumab (IFN-OCR). Adjusted annualised relapse rate (ARR) and time-to-onset of 24-week confirmed disability progression (CDP24) were analysed.ResultsAmong IFN-OCR patients, ARR decreased from 0.20 in the year pre-switch to 0.10, 0.08 and 0.07 at Years 1, 2 and 3 post-switch. OCR-OCR continuers maintained low ARRs through the year pre-OLE and the 3 years of OLE (0.13, 0.11, 0.08, 0.07). CDP24 was less frequent in OCR-OCR continuers versus IFN-OCR switchers in the year pre-switch and Years 1, 2 and 3 of OLE (7.7%/12.0%, 10.1%/15.6%, 13.9%/18.1% and 16.1%/21.3%; p<0.05, all comparisons).ConclusionsSwitching from IFN to ocrelizumab at the start of the OLE provided rapid reductions in ARR, maintained throughout the 3-year follow-up. After 5 years’ follow-up, patients who initiated ocrelizumab 2 years earlier accrued significant, sustained reductions in disability progression compared with patients switching from IFN.DisclosuresSponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Articulate Science, UK, and funded by F. Hoffmann-La Roche Ltd.
180 Cognitive diagnostic criteria lead to distinct patterns of functional connectivity in secondary progressive MS
Authors: Doshi Anisha , Castellazzi Gloria , Muhlert Nils , Alahmadi Adnan , Prados Ferran , Wheeler-Kingshott Claudia , Ciccarelli Olga , Chataway Jeremy 
Published: March 2023

Resting state functional MRI(rsfMRI) is an established tool for investigating cognitive impairment(CI) (affecting 40–70% dependent on criteria) in Multiple Sclerosis(MS). This study used rsfMRI to investigate the pattern of functional connectivity (FC) in cognitively impaired(CI) and cognitively preserved(CP) secondary progressive MS(SPMS) patients based on criteria.70 SPMS subjects (age54±7.1, disease duration 22±9.1 years, EDSS 6.0 (range 4.0–6.5), progression duration8.03±5.2 years) were recruited locally. Cognition was assessed by a battery of neuropsychometric tests and defined using the conservative criteria (z-score of -1.96 standard deviations (SD) on ≥2 tests) and lenient criteria (z-score of -1.5SDs on ≥2 tests). RsfMRI obtained using a 3T Philips scanner was pre-processed and underwent Independent Component Analysis(ICA) to identify the Resting State Networks(RSNs). Dual regression compared group-specific maps(i.e. CI vs CP according to criteria).We found that the proportion of SPMS-CI changes by 17.1% when using the more stringent conservative(30%) versus the lenient(47.1%) criteria. Overall, 14 RSNs were identified. The greatest FC differences between CI and CP patients within RSNs occurred with the conservative criteria. Independent of the CI criteria used, the left ventral attention network(LVAN), involved in attention processing, is overall the most impaired network in SPMS-CI suggesting that pathological changes in this RSN may underpin global cognitive problems in SPMS.
186 Familial multiple sclerosis: a community based epidemiological study in cumbria
Authors: Nwe May , Footitt David 
Published: March 2023

Multiple Sclerosis is an autoimmune inflammatory disease of the central nervous system. Recent studies have revealed that both genetic and environmental factors, principally latitude affect the prevalence.In Cumbria, the vast majority of multiple sclerosis patients are under the care of a single consultant and specialist nurse-led service. Being community-based we believe there are very few people with MS who are not known to the service and this makes the population especially suitable for epidemiological study. The fact that the clinical team has access to the whole GP record through a shared clinical record enhances the data available research.Nursing staff in the MS team have prospectively recorded the presence or absence of a family history of MS, and where present the affected family members. We will report upon the prevalence of a family history in our cohort of patients with MS, Clinically isolated syndrome and Radiologically syndrome which numbers 1300, of whom 1150 have an established MS diagnosis. We will compare this with expected rates of familial MS based upon a review of existing literature.
191 MOBILE/ENHANCE integrated efficacy analysis of PR-fampridine
Authors: Hupperts Raymond , Hobart Jeremy , Gasperini Claudio , Lycke Jan , Ziemssen Tjalf , Feys Peter , McNeill Manjit , Acosta Carlos 
Published: March 2023

IntroductionThe MOBILE and ENHANCE studies evaluated prolonged-release fampridine (PR-FAM) vs placebo (MOBILE, n=68 vs 64; ENHANCE, n=315 vs 318) in people with multiple sclerosis (PwMS) over 24 weeks. PR-FAM-associated improvements in walking and physical performance were assessed using an integrated efficacy analysis.MethodsPooled analyses of MOBILE/ENHANCE included the proportion of PR-FAM–treated PwMS with pre-specified threshold improvement in MSWS-12 and in Timed Up and Go (TUG) speed, and mean changes from baseline in MS Impact Scale physical subscale (MSIS-29 PHYS) and Berg Balance Scale (BBS).ResultsOver 24 weeks, significantly more PR-FAM–treated PwMS achieved ≥8-point mean improvement in MSWS-12 (44.3% vs 33.0%; OR: 1.68 [95%CI: 1.23, 2.29]; P<0.001) and ≥15% mean improvement in TUG speed (44.1% vs 34.5%; OR: 1.54 [95%CI: 1.13, 2.11]; P=0.007) vs placebo. Significant improvements from baseline were also registered in MSIS-29 PHYS (least square mean [LSM] difference: −3.18 [95%CI: −4.84, −1.52]; P<0.001) and BBS (LSM difference: 0.62 [95%CI: 0.09, 1.14]; P=0.021) vs placebo.ConclusionsThis post-hoc pooled analysis strengthens evidence that PR-FAM produces clinically meaningful improvements in self-reported walking and benefits self-reported physical function, mobility, balance, and quality of life over 24 weeks for PwMS.Support: Biogen. Disclosures to be included on poster.
206 Follow your nose to the diagnosis
Authors: Li Vivien , Vivekanandam Vinojini , Lunn Michael 
Published: March 2023

A 47-year-old female presented with episodic cranial neuropathies. Over four years, she had bilateral hearing impairment. Right maxillary distribution pain was attributed to sinusitis, with subsequent sinus surgery. She developed bilateral abducens palsies and left optic neuropathy, each lasting several weeks before resolution.She was diagnosed with hypopituitarism and commenced hormonal replacement after prolonged amenorrhoea. She noticed altered smell, and most recently, developed right facial weakness, which resolved with prednisolone.MRI brain demonstrated nodular dural thickening of cranial fossa floor, with symmetrical T2 white matter and basal ganglia hyperintensity. Bloods and CSF were non-diagnostic. FDG-PET showed multifocal uptake particularly involving the upper aerodigestive tract.Differentials included inflammatory or infiltrative aetiologies. Meningeal biopsy was considered, but recent corticosteroids and hydrocortisone replacement would potentially mask tissue appearances. A history of tonsillectomy and sinus surgery four years earlier coinciding with neurological symptoms led to re-review of external histology, showing 40% of IgG-positive plasma cells expressing IgG4. IgG4 disease was diagnosed and immunosuppression commenced, with clinical stability and radiological improvement.This case illustrates the chronic fluctuating presentation of IgG4 disease, and the forensic medicine required to make a diagnosis with relevant historical histology, when both presentation and tissue have been modified by steroid treatment.
209 ‘How rare do we dare’ – hickam’s dictum taken to the extreme
Authors: Bunting EE , Lunn MP 
Published: March 2023

Solitary CNS Lymphomatoid granulomatosis (LG), a rare lymphoproliferative disorder, was discovered in a patient collecting rare neurological disorders.A patient diagnosed with Charcot-Marie-Tooth type 4C (SH3CT2) and Myasthenia Gravis, treated with mycophenolate, presented with musical hallucinosis, described as choral music occurring in short bursts. Investigations deemed this secondary to hearing loss. Neuro-imaging revealed a cerebellar cavernoma and a developmental venous anomaly, thought to be incidental. A rapidly expanding, right frontal lesion was noted on subsequent imaging. Biopsy of this lesion revealed a florid inflammatory infiltrate composed of small lymphocytes, macrophages and non-caseating granulomata. Immunohistochemical staining for CD20 showed moderate numbers of B-lymphocytes, positive for Epstein Barr virus-encoded small RNA, suggesting a diagnosis of LG.Immunosupression is a risk factor for EBV mediated lymphoproliferative disorders. SH3TC2 is involved in myelination and maintenance of the node of Ranvier and mutations disturb interactions with the GTPase Rab11. Outside of the peripheral nervous system mutated Rab11 molecules are known to have neoplastic potential through prevention of the normal function of binding the oncogene Evi5, potentially explaining the development of LG as another rare disorder. Despite tenuous links, these rare neurological disorders appear unrelated in this individual.
212 Is there an ethnicity bias of access to MS services? The barts health experience revisited
Authors: Allen-Philbey Kimberley , Silveira Facundo , Turner Ben , Giovannoni Gavin , Schmierer Klaus 
Published: March 2023

IntroductionPrinciple 1 of the NHS constitution states that access to services should be non-discriminatory including ethnic background. Early diagnosis and initiation of disease modifying treatment (DMT) in people with multiple sclerosis (pwMS) is important for prognosis. We report findings from a re-audit of ethnic equity of clinical service experience in pwMS in east London.MethodsRetrospective cohort of pwMS ≥18 years old, diagnosed between 2014–2017 with 2 years of follow-up, attending Neurology services at Barts Health NHS Trust. We compared access to MS services between ethnic groups. Result variables included (i) first symptom to diagnosis (S2D) and (ii) diagnosis to DMT (D2T).Results59 pwMS fulfilled inclusion criteria, 7/59 were Black, 13/59 South Asian, 22/59 White and 17/59 as Other. There was a non-significant trend towards shorter S2D in White pwMS (1.2 years) compared to the other groups (Black 1.94, South Asian 1.93 and Other 1.55) (p=0.54). No difference was observed regarding D2T (Black 0.51 years, South Asian 0.31, White 0.58 and Other 0.47, p=0.25).ConclusionReassuringly, no ethnic inequity of access to MS services was detected, confirming findings of the original audit.
14.57 How much of anti-CGRP monoclonal antibody preventive therapy for migraine is contextual (Placebo) effect?
Authors: Forbes Raeburn B , McCarron Mark O 
Published: March 2023

BackgroundRandomised Controlled Trials (RCTs) of Anti-CGRP monoclonal antibodies prove their efficacy in preventing Episodic Migraine (EM) and Chronic Migraine (CM), but will cost c£350 per patient per month. Many headache interventions have significant placebo responses. The aim is to quantify the contribution of placebo and other non-specific effects by estimating the Proportion Contextual Effects from available RCTs.MethodsSearch of clinicaltrials.gov for RCTs in adults with EM or CM. Data extracted from peer reviewed publications, conference abstracts and company websites January 2013-Sep 2018. Primary outcome - Reduction in Monthly Migraine Days. Effect Size (Standardised Mean Difference - SMD) and Proportion Contextual Effect (Response Ratio) calculated with 95%CI. Risk of bias not estimated.Results56 registered studies identified, of which 28 were RCTs (8 incomplete or non-migraine and 2 in children). 18 included trials tested 19 doses of CGRP-antibody in EM and 9 doses in CM. Effect Sizes were small (SMD 0.2–0.49) in 12/19 EM and 7/9 CM doses, moderate (0.5–0.79) in 5/19 EM and 1/9 CM. Proportion Contextual Effects were between 50–70% in 13/19 EM and 8/9 CM doses, and >70% in 5/19 EM and 2/9 CM doses.DiscussionAnti-CGRP antibodies are effective treatments for EM and CM, but this is primarily due to contextual effects. >50% of the benefit accrued is attributable to health service personnel and infrastructure, not a direct drug effect.
214 Analysis of CSF IgG index, IgG synthesis and clinical presentation among CSF OCBs negative patients
Authors: Mihalova Tatiana , Kwong Jing Ling , Alachkar Hannah 
Published: March 2023

BackgroundMultiple sclerosis, an autoimmune condition, is characterised by high incidence of CSF positive oligoclonal bands (OCBs). Positive OCBs are now used for diagnosis of clinically definite MS. The clinical course of CSF OCBs negative neurological patients can differ.MethodFrom total of 987 CSF OCBs negative samples, processed in immunology laboratory 2015–2016, 76 CSF OCBs negative samples have shown other CSF abnormalities – raised CSF IgG index, raised CSF IgG synthesis and reduced blood brain barrier ratio (BBBR). We retrospectively reviewed their clinical presentation, CSF protein, WBC and CSF IgG index, IgG synthesis and BBBR.Results4 distinctive clinical groups were identified: inflammatory peripheral nerve disease, neurosarcoidosis, other CNS inflammatory disorders (SLE, vasculitis, ADEM, MS) and degenerative disorders.CSF OCBs negative patients with neurosarcoidosis presented with significantly raised CSF protein (on average 1.76 g/dl), CSF IgG synthesis (125.3), and IgG index (0.995) and low BBBR (33). Other CNS inflammatory disorders had mildly raised CSF protein (0.74 g/dl), IgG synthesis (30), IgG index (0.835) and reduced BBBR (70), but not as significant as seen in neurosarcoidosis.ConclusionThe distinctive CSF pattern despite of negative CSF OCBs may be helpful if suspecting diagnosis of neurosarcoidosis, hence performing CSF IgG synthesis and IgG index may be helpful.
215 Demographic, clinical and paraclinical features in a subgroup of patients with NMOSD
Authors: Wegehaupt Thomas , Vundavalli Sriram , Cooper Sarah , Leite Maria , Palace Jacqueline , Fisniku Leonora 
Published: March 2023

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is an autoimmune, inflammatory condition more commonly distinguished from multiple sclerosis (MS). Early diagnosis is paramount as NMOSD and MS respond to different immunomodulatory therapies.ObjectiveTo determine common clinical and paraclinical features at the disease onset of NMOSD-patients.MethodsAll antibody-positive NMOSD-patients seen between 2013 and 2017 at Brighton and Sussex University Hospital were included. Their clinical and paraclinical data at the first presentation was reviewed.Results9 patients were included; 8 caucasians; 5 females. Mean age at the onset was 48.8 years. All MOG-positive patients (5/9) presented with optic neuritis; AQP4-positive patients (4/9) presented with transverse myelitis or area postrema syndrome. One patient (AQP4-positive) had an underlying malignancy. Three patients had positive oligoclonal bands. None fulfilled the McDonald radiological criteria for MS. Brain MRI scan was abnormal in 5/9 patients with the lesions being either juxtacortical or subcortical but none periventricular. Spinal cord lesions were 2 or more vertebral length (range 2 – 10) and were isotense. No silent spinal cord lesions were seen. One patient required more than one immunosuppression (AQP4-positive) and one (MOG-positive) was on none.ConclusionEarly recognition of NMOSD-patients is important in order to direct appropriate treatment.
216 Retinitis pigmentosa and autoimmunity
Authors: Mihalova Tatiana , Pankhania Kishan , McKee David 
Published: March 2023

BackgroundRetinitis pigmentosa (RP) is a genetic disorder with affected gene expressed in rod cells, ultimately leading to death or secondary degeneration of cone cells. Over 170 genes have been associated with RP, but little is known of HLA gene association. Research has suggested link between RP and other autoimmune diseases. MS is a known autoimmune disorder with most important genetic factor being HLA-DRB1*15:01. Primary angiitis of central nervous system is an autoimmune disorder of vessels leading to inflammation and ischaemia. Several genetic associations in the HLA region have been described with systemic vasculitides.Methods2 non-related patients with established retinitis pigmentosa and with similar neurological presentation and neuroimaging were reviewed. First patient diagnosed with primary angiitis of CNS was treated with Mycophenolate (steroid-sparing agent), second patient had rapidly evolving severe relapsing remitting MS treated with Natalizumab. Genetic analysis was performed by HLA typing and 170 retinal genes panel.ResultsThere was no genetic overlap in the positive retinal genes or HLA-A, B and DRB1 regions. Both patients expressed HLA-C*07 and HLA-DQB1*03 alleles. Patient with vasculitis expressed HLA- DRB1*15:01 and patient with MS expressed HLA-DRB1*03:01 and DRB1*04:04. Results suggest a possible link between RP and autoimmunity as both had HLA-C*07 and HLA-DQB1*03 alleles. Initially both patients were treated with steroids and had a good neurological response.
219 First year of the early access to medicines scheme for raxone in duchenne muscular dystrophy
Authors: Lawrence Catherine , Hasham Shabir 
Published: March 2023

Raxone (idebenone) received the first positive scientific opinion for a treatment option in DMD for inclusion into the Early Access to Medicines Scheme (EAMS) in June 2017.EAMS is regulated by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) and aims to provide earlier availability of promising new unlicensed medicines to UK patients that have a high unmet clinical need.The first patient was enrolled 12 weeks after the scheme approval. In the first year of the scheme forty-six patients were able to access Raxone in six centres. Ease of implementation of the scheme across the NHS was variable. In addition to the MHRA positive scientific opinion, and supportive guidance issued by NHS England and Scotland, most clinicians were required to obtain local hospital committee approvals before entering the scheme, which introduced delays in patient enrolment. Local knowledge of EAMS, its objectives and stakeholder responsibilities, was found to be limited and also contributed to delays in implementation and inequality of access.Under EAMS Raxone is administered under routine clinical practice. In the second year additional data collection has been introduced to obtain information on the effectiveness of the use of Raxone in an environment similar to that which would exist if the medicine receives a future marketing authorisation for DMD.
221 Quality improvement project: updating the muscle biopsy referral form
Authors: Sarkar Pamela , Atton Giles , Urankar Kathryn , Long Nicola , Patel Jennifer , Smart Joanne , Brady Stefen 
Published: March 2023

When reconfiguring the muscle biopsy service at our hospital, it became apparent that the referral form used was inadequate. The clinical information acquired was minimal. The form did not comply with National Coding practice.1The absence of good clinical information could negatively affect the neuropathological diagnosis and income generated by the muscle biopsy service. Therefore, in collaboration with Neuropathology and Clinical Coding, we developed a new form to capture relevant clinical and coding information. To determine the impact of the new referral form, we undertook a quality improvement project.Forty muscle biopsies (2012–2016) were selected at random from the Neuropathology archives. The notes were reviewed and used to complete the new referral form. Using this information, the coding and tariffs were reassessed and compared to those produced using the original referral form. Prospective data from muscle biopsy cases (01–06/2018) were also analysed.Results demonstrated a significant improvement in quality of documentation supplied to Clinical Coding and increased diagnostic usefulness for Neuropathology. Although the new form has significantly helped the Clinical Coding team, with a simpler and more efficient coding outline that has reached National Coding Standards1, it had little impact on the income generated.References‘National Clinical Coding Standards ICD-10 5th Edition 2017 -https://hscic.kahootz.com/gf2.ti/f/762498/27838213.1/PDF/-/NCCSICD102017.pdf
222 Investigating directionality of neurodegeneration in vivo in ALS using multimodal MRI
Authors: Toh Charmaine L , Keslake Andrew , Harding Joseph , Baster Kathleen , Hoggard Nigel , Bigley Julia , McDermott Christopher J , Shaw Pamela J , Wilkinson Iain D , Jenkins Thomas M 
Published: March 2023

BackgroundThe anatomical location of the earliest damage in amyotrophic lateral sclerosis (ALS) is still debated. Two main competing hypotheses have been proposed: the dying-forward hypothesis states the damage occurs in the precentral gyrus (PCG) and spreads caudally, which is in contrast with the dying-back hypothesis. This study aims to address this question of directionality of neurodegeneration in vivo using a multimodal neuroimaging approach to derive measures of damage of the motor pathway and analyse them in a common domain.MethodsMRI was performed on 78 ALS patients and 13 controls. PCG thickness was derived from using FreeSurfer, corticospinal tract (CST) fractional anisotropy (FA) from diffusion tensor imaging using FSL, and axial C3 cord area estimates using Philips online software. Comparisons between patients and controls were reported using unpaired t-tests. Parameter estimates were converted to z-scores, referenced to control data, plotted from PCG through CST to cord and directionality of damage assessed by fitting a mixed-effects linear regression model.ResultsZ-scores were not significantly different between PCG and FA (0.24,[95%CI -0.13,0.61], p=0.208) but were significantly lower in FA compared to cross-sectional cord area (-0.85,[95%CI -1.25,-0.46] p<0.001).DiscussionThis novel multimodal imaging approach supports a dying-forward neurodegenerative process in ALS.
223 Anderson tawil syndrome: expanding the phenotype and assessing cardiac risk
Authors: Vivekanandam Vinojini , Savvitis Konstantinos , Pattni Jatin , Fialho Doreen , Hanna Michael G , Matthews Emma 
Published: March 2023

Anderson Tawil Syndrome (ATS) is a rare channelopathy traditionally characterised by periodic paralysis, cardiac arrhythmias and dysmorphic features. Mutations in the KCJN2 gene have been associated with ATS. Accurate and early diagnosis is important in facilitating treatment of episodic paralysis and preventing potentially life-threatening cardiac events.We aim to fully characterise the phenotype in a carefully stratified cohort including cognitive deficits and cardiac risk.66 patients were identified with KCJN2 mutations. Comprehensive clinical information was available for 18 of these patients. Cardiac symptoms were prominent. Two thirds (11) had daily or very frequent palpitations. 27% (5) reported shortness of breath. Serious cardiac complications occurred in 4 patients (ICD insertion, left ventricular dysfunction/cardiomyopathy). 39% (7) reported pain which has previously not been appreciated as part of ATS. Interestingly, 4 patients had fasciculations. 4 patients had minimal decrement (<48%) on Long Exercise Tests (LET) despite having episodic weakness. Lower limb Muscle MRI was abnormal in 6 patients. Excess sleepiness was reported. Neuropsychometric testing suggests slowed processing speed. While dysmorphic features exist, these can be subtle. Short stature is not ubiquitous. Heterogeneity within families was commonly seen.The phenotypic spectrum of ATS is broader than currently appreciated, and data analysis is ongoing.