bluuebunny/crossref_metadata_2025_split huggingface dataset:
192 Does socioeconomic status impact on the prescription of disease-modifying treatments in people with multiple sclerosis?
Authors: Reyes Saúl , Allen-Philbey Kimberley , Suarez Sebastian , Yildiz Özlem , Turner Ben , Gnanapavan Sharmilee , Schmierer Klaus , Marta Monica , Mathews Joela , Giovannoni Gavin 
Published: March 2023

ObjectiveTo examine the association between socioeconomic status (SES) and prescription of disease-modifying treatments (DMTs) in people with multiple sclerosis (pwMS).MethodsA cross-sectional study was conducted among 734 pwMS aged ≥18 years attending the neuroinflammation service at The Royal London Hospital (Barts Health NHS Trust) between 1997 and 2017. SES was determined by patient income and education extracted from the English Index of Multiple Deprivation. Multinomial logistic regression was performed to assess differences between SES and prescription of DMTs.ResultsDMTs were categorized as follows: moderate efficacy therapies included Glatiramer Acetate and Beta-Interferons (n=81, 11.04%), high efficacy therapies included Cladribine, Fingolimod and Dimethyl Fumarate (n=409, 55.72%), and very-high efficacy therapies included Natalizumab and Alemtuzumab (n=244, 33.24%). Medians for income and education deciles were 4 (IQR 3–7) and 6 (IQR 4–8), respectively. Patient income was not associated with increased odds of being prescribed high efficacy (OR, 1.02; 95% CI, 0.91–1.14; p=0.814) or very-high efficacy DMTs (OR, 1.01; 95% CI, 0.90–1.14; p=0.732). Similarly, patient education was not associated with the prescription of high efficacy (OR, 0.96; 95% CI, 0.84–1.10; p=0.585) or very-high efficacy DMTs (OR, 0.96; 95% CI, 0.84–1.10; p=0.538).ConclusionsSES was not predictive of prescription of DMTs in this single-centre study. It would be of interest to compare our data with other MS services, and to map these results onto the inequity in access to DMTs across the UK.
194 Natalizumab treatment for MS: UK and global results from TOP
Authors: Nicholas Richard , Harrower Timothy , Jiang Xiaoyu , Licata Stephanie , Vonsy Jean 
Published: March 2023

IntroductionThe TYSABRI Observational Program (TOP) is the largest real-world study in natalizumab-treated relapsing-remitting MS patients. Country-specific data, alongside global data, can provide information on natalizumab’s effectiveness in local practice.MethodsAnnualised relapse rate (ARR) and cumulative probability of 24-week confirmed disability worsening (CDW; Expanded Disability Status Scale [EDSS] score increase from baseline of ≥1.5 from 0.0, ≥1.0 from 1.0–5.5, or ≥0.5 from ≥6.0) and improvement (CDI; decrease ≥1.0 from baseline EDSS score ≥2.0) over 6 years were analysed in TOP UK (n=134) and global (N=6149) cohorts using data from July 2007 to November 2017.ResultsARR decreased in UK patients from 2.21 in the year before initiation to 0.21 on natalizumab, paralleling the global decrease from 1.99 to 0.21. At 6 years, probabilities of CDW and CDI were, respectively, 27.8% and 34.4% in UK patients and 24.2% and 32.0% globally.ConclusionsConsistent with global TOP results, natalizumab ARRs and disability worsening rates remained low and disability improvement rates exceeded 30% at 6 years in the UK cohort. These results support natalizumab’s long-term effectiveness in real-world settings.Support: Biogen. Disclosures will be included on the poster.
195 MS disease modifying therapy (DMT) sequencing – tysabri to mavenclad de-escalation in JC-virus positive MS patients
Authors: Mihalova Tatiana , Vernon Karen , Sharaf Nazar , Talbot Paul , Rog David 
Published: March 2023

BackgroundThere is a significant UK variation in the DMT sequencing strategies for high PML risk patients on Tysabri. In Greater Manchester Neuroscience centre we gradually reduced the number of high PML risk patients on Tysabri from 89 in 2016 to 26 in 2018. From our experiences de-escalation strategy from Tysabri to Fingolimod or Lemtrada seemed safe. Fingolimod, less efficacious switch, tends to be delivered quicker than Lemtrada (requiring lesser safety checks), but the efficacy of Lemtrada in MS patients with disease duration >10 years remains uncertain.MethodBetween January 2018 and November 2018 we switched 14 high risk PML patients from Tysabri to Mavenclad. All patients underwent MDT discussion, lumbar puncture with JCV PCR and MRI checks prior to DMT switch.ResultsWe present the first UK MS patient cohort de-escalating from Tysabri to Mavenclad. Older (average age of 44) and more disabled patients (average EDSS=4.75) opted for Mavenclad, with equal gender distribution (7:7). Average disease duration was 7.5 (2–10) and patients received 52 (6–107) Tysabri infusions. 5 patients had other DMTs prior to Tysabri (5 Copaxone, 1 Rebif, 1 Tecfidera), 9 patients had Tysabri as their first DMT. Average JC-virus serology titer was 1.86.ConclusionSwitching high PML risks patients from Tysabri to Mavenclad appears to be well tolerated; regular MRI monitoring showed no PML carry-over risk and no significant MS disease activity.
199 Changes in natalizumab exposure and PML incidence over time
Authors: Giovannoni Gavin , Kappos Ludwig , Berger Joseph , Cutter Gary , Fox Robert , Wiendl Heinz , Chang Ih , Kasliwal Rachna , Lee Lily 
Published: March 2023

IntroductionSince the identification in 2012 of three risk factors for natalizumab-associated progressive multifocal leukoencephalopathy (PML), changes in the PML incidence rate have been of interest.MethodsThe incidence of confirmed PML cases in Biogen’s postmarketing global safety database from November 2009 to November 2017 was evaluated retrospectively. Overall incidence in natalizumab-exposed patients was determined by the estimated total number of patients exposed and the number of confirmed cases. Changes in exposure patterns over time were evaluated by 12-infusion epochs.ResultsAs of 30 November 2017, 180,656 patients worldwide had received ≥1 dose; overall natalizumab-associated PML incidence was 4.19/1000 patients. Since mid-2016, overall monthly incidence of PML appears to have stabilised, remaining between 4.18 and 4.24/1000. PML incidence was greatest in later, higher risk infusion epochs (≥37 infusions). The relative increase in the proportion of patients in higher-exposure epochs (>24 infusions) has declined from 2013 to 2017.ConclusionsThe stabilisation of overall natalizumab-associated PML incidence beginning mid-2016 coincides with the introduction of a new risk algorithm, suggesting that risk stratification factors are being incorporated into clinical practice and may continue to impact future incidence.Support: Biogen. Disclosures to be included on poster.
200 AFFINITY: opicinumab in a targeted population of MS patients
Authors: Zhu Bing , Calabresi Peter A , Giovanonni Gavin , Kapoor Raj , Naismith Robert , Hartung Hans-Peter , Arnold Douglas L , Wolstencroft Paul , Johnson Kristina 
Published: March 2023

IntroductionOpicinumab is a human monoclonal antibody against LINGO-1, a negative regulator of oligodendrocyte differentiation and axonal regeneration. The phase 2 SYNERGY study identified a patient subpopulation with a potentially enhanced response to opicinumab treatment.MethodsAFFINITY (NCT03222973) is an ongoing, randomised, double-blind, placebo-controlled phase 2 study to evaluate the efficacy/safety of opicinumab vs placebo as an add-on to disease-modifying therapies in a targeted population. Inclusion criteria include: age 18–58; relapsing multiple sclerosis (MS) with ≤20-year duration; Expanded Disability Status Scale (EDSS) score 2.0–6.0; evidence of disease activity within 24 months prior to enrolment; brain MRI criteria suggestive of low myelin content but preserved tissue integrity in pre-existing T2 lesions; stably treated ≥24 weeks with interferon-beta, dimethyl fumarate, or natalizumab. Primary endpoint is the multicomponent Overall Response Score (based on EDSS, Timed 25-Foot Walk, and 9-Hole Peg Test). Secondary endpoints will evaluate confirmed improvement in disability measures.ResultsEnrolment began in September 2017 and was completed in September 2018. Participant baseline demographic, disease, and MRI characteristics will be presented.ConclusionsAFFINITY will further investigate the efficacy and safety of opicinumab in a subpopulation of MS patients.Support: Biogen. Disclosures to be included on poster.
14.45 Maintenance of idebenone treatment results in continued improvement in LHON patients
Authors: Lloria Xavier , Silva Magda , Lawrence- Catherine , Rudolph Guenther , Lob Felice , Livonius Bettina von , Catarino Claudia , Klopstock Thomas 
Published: March 2023

PurposeLHON is a mitochondrial disorder leading to progressive, irreversible loss of visual acuity (VA). Here we report on the long term treatment outcomes in real world clinical practice in which we evaluated the efficacy and safety of idebenone.MethodsPatients were treated with idebenone as part of an Expanded Access Program. Efficacy was assessed as a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS). CRR defined as improvement from off-chart to reading 5 letters on the ETDRS chart, or improvement of 10 letters. CRS is defined as maintenance of VA <1.0 logMAR (20/200).ResultsData from 111 patients was collected.The majority of patients (72.4%) had severe vision loss (>1.0 logMAR). A subset of 24 patients presented with VA <1.0 logMAR, and 50% of these experienced a CRS. CRR at last observation was achieved in 47.1% of patients after a mean of 10 months. For patients achieving CRR, 90.2% (37/41) had done so by 24 months. Mean of magnitude of CRR at last observation was more than seven lines on the ETDRS chart. The safety profile of idebenone in this longer term analysis was consistent with previous reports.ConclusionsIdebenone is well tolerated and effective in a large proportion of patients. Maximal patient benefit may be achieved by early initiation of treatment, and by prolonged treatment.
201 Alemtuzumab related HPV infection and cervical dysplasia: real world data
Authors: Ruffer Giles , Koniotes Anna , Warren Catherine , Bozzali Marco , Fisniku Leonora 
Published: March 2023

BackgroundAlemtuzumab a disease-modifying-therapy for relapsing-remitting Multiple Sclerosis (RRMS) increases the risk of Human Papilloma Virus (HPV) and cervical dysplasia. Annual HPV-screening is recommended in the Summary of Product Characteristics. 2018 Public of Health cervical screening programme in the United Kingdom recommends no more than three-yearly screening.ObjectiveTo assess HPV infection rate and cervical dysplasias in RRMS-Alemtuzumab-treated patients at Brighton and Sussex University Hospital.MethodReview of the cervical screening of Alemtuzumab-treated RRMS female-patients who had received at least one treatment course from March 2015 until January 2019.ResultsThe mean age of 80 female-patients who received Alemtuzumab was 39.1 years. Pre-treatment, 4/80 (5%) patients had a degree of dyskaryosis; 1/80 (1.25%) was HPV-positive. At one-year 5/72 (6.9%) patients who completed and had normal pre-treatment screening had abnormal cervical screening with 1/72 (1.39%) being HPV-positive. No extra HPV-positive cases were seen in year 2 (21-patients) and 3 (7-patients).ConclusionIn Alemtuzumab-treated RRMS-patients, rate of HPV infections and cervical dyspasias are comparable to epidemiological studies. Whereas it is important that women engage with the national cervical screening, more frequent screening may not be justified. Additional testing might not be of any benefit and might be a source of anxiety for the patients.
203 Infectious-like presentation of neuromyelitis optica with pyrexia and CSF lymphocytosis
Authors: Cheema Sanjay , Leddy Sara , Wickremaratchi Mirdhu 
Published: March 2023

A 19-year-old Philippine lady presented with persistent pyrexia over 39°C, abdominal pain and back pain. Over three days she then developed paraesthesia in all four limbs, proximal weakness in both legs, and sphincter disturbance. Vision was normal.Spinal cord MRI showed signal change and oedema from C2 to T12. CSF showed a lymphocytosis of 200 cells/mm3and protein of 1.0 g/L, with normal glucose.She was persistently febrile and was investigated extensively for an infectious myelitis and empirically treated with acyclovir and ceftriaxone. She made some improvement over the next two weeks and CSF lymphocyte count fell to 25 cells/mm3.T-SPOT was positive indicating latent Tuberculosis. CT body imaging was normal.Aquaporin-4 antibodies were positive. She was treated with high dose steroids, and mycophenolate was started after 3 months of anti-tuberculous medications. She went on to make a full neurological recovery.The persistent pyrexia was likely centrally generated due to high aquaporin-4 expression in the hypothalamus. This and the significant CSF lymphocytosis mimicked an infectious presentation and led to a late diagnosis and treatment with immunosuppression.
204 Therapeutic plasma exchange for neurological disorders: the experience of a tertiary neuroscience centre
Authors: Parker Sarah , Das Joyutpal , Hewamadduma Channa 
Published: March 2023

The role of Therapeutic plasma exchange (TPE) in immune-mediated neurologic disorders is expanding. Our experience with TPE at a tertiary neuroscience centre is reported.Medical records of all patients who received TPE between 2013 and 2018 at Sheffield Teaching Hospitals NHS Foundation Trust were reviewed. The procedure involved the removal of 1–1.5 plasma volumes and replacement with isotonic 4.5% human albumin solution. A typical cycle consisted of 5–7 procedures within 14 days.A total of 66 patients received 478 TPE procedures over 76 therapeutic cycles. TPE was performed for 16 neurological indications including multiple sclerosis (34.8%), Guillain-Barre syndrome (13.6%) and neuromyelitis optica spectrum disorder (9.1%). 78.8% of patients received TPE for category I or II indications according to The American Society for Apheresis (ASFA) guidelines. 73.8% of patients in our cohort demonstrated neurological improvement following TPE. 21.2% of patients responded to TPE administered for indications outside the ASFA guidelines. There was no treatment related mortality. Complications associated with TPE included bacteraemia, pulmonary embolism, deep vein thrombosis and bacterial endocarditis.Our data suggests that TPE was associated with favourable outcomes. Further studies are required to assess the efficacy of TPE in those conditions for which there is currently little evidence.
207 An atypical cause of longitudinally extensive transverse myelitis after an allogeneic haemopoietic stem cell transplant
Authors: Kemp Michael , Keh Yann Shern , Dayanandan Rejith , Saif Muhammad , Nixon John 
Published: March 2023

We present an unusual case of longitudinally extensive transverse myelitis (TM) with atypical features following allogeneic stem cell transplant.A 53 year old male with a history of allogeneic stem cell transplant (SCT) two years earlier for myelofibrosis presented with a two day history of difficulty walking. Clinically he had a left Brown-Sequard syndrome. MRI showed a cord lesion preponderant to the left anterior quadrant at T7-9.Initially independently mobile he rapidly deteriorated over two days, a week following admission, developing a dense flaccid paraparesis with a sensory level to the costal margin. Repeat imaging showed diffuse cord signal change from C6 downwards. In addition a persistent fever and rash emerged. Treated with high dose steroids and plasma exchange, the clinical course has progressed no further and rehabilitation continues however imaging has shown significant improvement.Whilst there are case reports of TM after allogeneic SCT, they’ve typically responded quickly to immunosuppressive treatment which we have not yet seen. There was no active graft versus host disease at the time of presentation which makes this to be an unlikely cause of this presentation. This case highlights the lack of detailed cases and imaging of similar reported presentations.
208 Immune checkpoint inhibitor-related neurotoxicity: a case series
Authors: Brown Rachel , Au Lewis , Spain Lavinia , Furness Andrew , Rees Jeremy , Rossor Alex , Morris Emma , Zandi Michael , Lunn Michael , Larkin James , Turajlic Samra ,   on behalf of EXACT consortium, Carr Aisling 
Published: March 2023

Immune checkpoint inhibitors (ICI), monoclonal antibodies enhancing T cell responses against tumour cells, have revolutionised the treatment of cancers such as advanced melanoma, leading to enhanced survival. Their action, however, is not tumour-specific, and patients can develop multisystem immune related adverse events (irAE). Neurological irAEs have been reported in 1–14% of patients, depending upon the ICI used, and can affect any part of the neuro-axis. A recent case series from the Royal Marsden Hospital (RMH) identified 10 patients with neurotoxicity following ICI for advanced melanoma between 2010–15, specifically neuropathy (6), plexopathy (1) and aseptic meningitis (3). Exactly how neurological injury occurs, whether cell-, cytokine- or antibody-mediated, is unknown.We present early data from a newly established collaboration with RMH, aiming to clinically characterize these patients, and identify the cause of neurological injury. To date, we have advised on patients (age range 53–80) with myositis, Guillain-Barré (GBS)-like neuropathy, plexopathy, aseptic meningitis, and encephalitis following ICI (ipilimumab and/or nivolumab) for advanced melanoma. Features common to these patients include their subacute onset, time from ICI administration, and steroid responsiveness (including in GBS-like cases). The incidence of neurological irAEs following ICI will rise with increasing use, and is therefore of concern to practicing neurologists.
210 CASPR2 antibody-related movement disorders: case series
Authors: See Mei , Cahill Varduhi , Scotton Sangeeta , Newman Piers , Sadalage Girija , Cherian Ajith , Divya KP , Jacob Saiju 
Published: March 2023

IntroductionContactin-associated protein 2 (CASPR2) antibodies are implicated in the development of a spectrum of neurological conditions where movement disorders constitute a substantial part of the clinical manifestations along with behavioral and cognitive impairment.Case reportWe report a case series of three patients presenting with a variety of clinical phenotypes associated with choreoathetoid movement disorder, camptocormia and myoclonus. All three patients, in addition to motor manifestations, exhibited a degree of cognitive impairment. One patient was severely debilitated with florid choreoathetoid movements and prominent behavioral disturbance impacting upon daily living. In the other two patients, worsening camptocormia and myoclonus resulted in the loss of ambulation. Their atypical clinical manifestations necessitated an extensive diagnostic workup with the exclusion of neurodegenerative and paraneoplastic causes. Not uncommonly, the possibility of a functional neurological disorder was also raised. The diagnosis was reached with the detection of CASPR2 antibodies in serum and CSF. The causative relationship between CASPR2-antibodies and the clinical manifestations was further substantiated by the good response to immunological therapies including steroid treatment, intravenous immunoglobulin and therapeutic plasma exchange.ConclusionThe spectrum of CASPR2-associated movement disorders continues to rapidly expand. Increased awareness amongst clinicians is necessary for a timely diagnosis and treatment initiation.
213 ‘Taking the brakes off’- immune checkpoint inhibitor induced neurotoxicity
Authors: Porter Marie-Claire , Papa Sophie , Carroll Paul , Williams Victoria 
Published: March 2023

Immune checkpoint inhibitors have greatly improved the survival of patients with advanced melanoma and are now becoming standard therapy for treating a wide range of different forms of cancer. Although immune mediated neurological complications related to these drugs are reported to be uncommon, occurring in around 1% patients, with the increased use of these treatments, there are likely to be more cases of neurotoxicity recognised in patients receiving cancer immunotherapy.We present a case series of 6 patients, seen in our trust, who developed a range of neurological complications associated with immune checkpoint inhibitor use. The conditions we encountered were:Myasthenia gravis, autoimmune encephalitis, aseptic meningitis and hypophysitis in 4 patients diagnosed with advanced melanoma treated with both single and combined immunotherapyCerebellar ataxia, that re-occurred with each immunotherapy treatment for oesophageal cancerWorsening of migraine with the commencement of treatment for bladder cancerThese cases illustrate the diverse adverse effects that these drugs can have on both the peripheral and central nervous system and the sometimes complex management required to treat them. We discuss the guidelines for treatment of immune checkpoint inhibitor neurotoxicity and the importance of recognising these conditions.
218 Management strategies for neuroimmunological complications following treatment with immune checkpoint inhibitors
Authors: Bose Smriti , Sumangala Salini , Steven Neil , Jacob Saiju 
Published: March 2023

ObjectiveThe use of immune checkpoint inhibitors (CIs) for malignancies has revolutionised oncological management in the last few years. These agents are known to cause immune-mediated complications in various systemic organs. The neurological complications of these are now being increasingly recognised. The cases managed in our institution where there were neuroimmunological complications following CIs were reviewed. We discuss management strategies for early recognition and treatment, thus minimising morbidity.MethodA joint effort by neurologists and medical oncologists to review clinical practice guidelines for management of neurological adverse effects of checkpoint inhibitors. This was based on a review of several cases reported, as well as experience from all the cases managed in our hospital.ResultsThere are no British guidelines from the neurological perspective for early identification of symptoms. Guidelines are based on expert consensus and also on treatments reviewed from literature.ConclusionRecommendations advice early identification of signs and symptoms followed by grading them as mild, moderate and severe (grades 1, 2, 3). Grade 1 symptoms require continuation of the CIs and symptomatic management. CIs should be stopped temporarily for grade 2 and permanently for grade 3 symptoms. Steroids plasma exchange, IVIg would be the first line of treatment.
15.09 Examining the neurological consequences of new psychoactive substances -‘legal highs’
Authors: Jones Rebekah , Kelleher Charles , Tanti Matthew , Cosgrove Jeremy , Maguire Melissa 
Published: March 2023

BackgroundNew psychoactive substances (NPS) are of global concern accounting for increasing deaths in the UK. We conducted a retrospective analysis of patients attending Leeds Teaching Hospitals NHS Trust with NPS abuse during 2016–2017 and report neurological presentations and outcomes.MethodsWe identified 227 records of NPS attendances through electronic searches using Symphony electronic software. Demographic and clinical data were obtained from case-note review.ResultsAverage age was 34, 82% were male. Two thirds were unemployed, 17% prisoners, 9% students and 4% prison workers. ‘Spice’ accounted for the majority of presentations (90%). 4-methyl methcathinone (‘MCAT’) accounted for 8% of presentations. The remainder reported nitrous oxide (NOS) use. In the spice subgroup, 52% had low GCS, 20% had seizures. Ventilatory support was required in two cases (1%). In the MCAT subgroup, average GCS was 14 and 20% of patients presented with seizure. Psychiatric disturbance was higher in MCAT group (30%). Most patients (62%) were observed in the emergency department and then discharged. Only 3% were referred to the drug and alcohol team.ConclusionsSpice accounted for the majority of NPS presentations. Unemployed single men were particularly at risk. Low GCS and seizures were the commonest presentations, with most requiring observation only.