bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of COVID-19 vaccines in multiple sclerosis patients receiving disease-modifying therapies in England
Authors: Garjani Afagh , Patel Sameer , Law Graham R , Bharkhada Dhiren , Rashid Waqar , Coles Alasdair , Evangelou Nikos 
Published: August 2022

Studies have measured the immunological response to COVID-19 vaccines among multiple sclerosis (MS) patients receiving disease-modifying therapies (DMTs), but its clinical relevance is unclear. We aim to understand how MS DMTs affect the clinical effectiveness of COVID-19 vaccines.We analysed data of all MS patients receiving DMTs in England from December-2020 to January-2022. We calculated post-vaccination (≥14 days following second dose) incidence of infection (positive COVID-19 test) and COVID-19 related hospitalisation (within 0-28 days of a positive test and >1 day). We used merged datasets of the NHS England and NHS Improvement and the UK Health Security Agency.A total of 38,039 MS patients on DMTs (90%) had at least two COVID-19 vaccines. Post-vaccination incidence of infection was 24% (859/3624) for ocrelizumab, 22% (819/3797) for fingolimod, and ranged from 11% to 16% for other DMTs. Hospitalisation rate among infected patients was 7% (n=61) for ocreli- zumab, 4% (n=33) for fingolimod, and ranged from 1% to 4% for other DMTs.Patients on ocrelizumab have higher rates of COVID-19 related infection and hospitalisation compared to other DMTs using current vaccination protocols. Patients on fingolimod also have higher rates of post- vaccination infection but their hospitalisation rate is similar to other DMTs. Further analysis including demo- graphics, booster vaccines, unvaccinated, and mortality is ongoing to be presented at the meeting.
171 Urinary P75: a novel biomarker for motor neuron disease?
Authors: Chapman Laura , Shepheard Stephanie , Verber Nick , Turner Martin , Malaspina Andrea , Rogers Mary-Louise , Shaw Pamela 
Published: August 2022

Motor neuron disease (MND is a progressive and fatal disease. The urinary neurotrophin receptor p75 extracellular domain (p75ECD) has previously been reported as a potential disease biomarker.This study measured urinary p75ECD using an enzyme-linked immunoassay and normalised the results against urinary creatinine. Participants were recruited via the Multicentre Biomarker Resource Strategy in ALS (AMBroSIA) programme. Study participants included 97 MND patients, 24 of whom were studied longitudinally, and 27 healthy controls. The longitudinal changes in disease severity and survival in com- parison to urinary p75ECD were examined using mixed-model analysis on SPSS.Confirming previous findings, urinary p75ECD levels were significantly higher in patients with MND (median 6.78ng/mg) compared to controls (4.57ng/mg) at first study visit (p=0.013). There was a significant negative correlation between ALSFRS-R rating and p75ECD levels (p=<0.001), indicating that an increase in the severity of motor neuron injury correlated with an increase in p75ECD levels. There was a significant increase in p75ECD between first and second samples in the same participants, indicating an increase in the level of this biomarker longitudinally during the disease course (p=0.011).Urinary p75ECD is a strong candidate as a biomarker which increases with disease progression, and which has potential as a pharmacodynamic biomarker.
172 Impact of age on interventions and survival in people with motor neuron disease in Scotland
Authors: Christides Alexander , Symonds Alexander , Johnson Micheala , Beswick Emily , Newton Judith , Chandran Siddharthan , Pal Suvankar , Consortium CARE-MND 
Published: August 2022

IntroductionMotor neuron disease (MND) is rapidly progressive and largely fatal. The National Institute for Health and Care Excellence guidelines (2016) outline best practice for symptomatic interventions including riluzole, gastrostomy, and non-invasive ventilation (NIV). We aimed to investigate the impact of age on interventions and survival in MND using data from the Scottish MND register (CARE-MND), hypothesising these factors may be impacted by increasing age.MethodsWe interrogated the CARE-MND database for incident cases in Scotland diagnosed between 01-Jan-2015 to 31-Dec-2020. Survival was compared in different age cohorts using Kaplan-Meier curves and log-rank test. Management was compared in different age cohorts using Chi-squared test.Results828 individuals were included (median age at diagnosis 68.7 years (interquartile range 61.4-76.1)). We investigated age cohorts of <40, 40-60, 60-80, and >80 years. Median survival from diagnosis in each cohort was 24 months, 18 months, 11 months, and 4.5 months respectively (p<0.001). Riluzole, NIV and gastrostomy were implemented least in the oldest group (p<0.05).ConclusionsOur data supports reduced survival of MND with increasing age, together with lower rates of riluzole prescribing, NIV use, and gastrostomy insertion, and offer insights into how care may be optimised in line with national guidelines.
176 Motor fatigability in motor neuron disease
Authors: Sassani Matilde , Alix James , Baster Kathleen , Cercignani Mara , Shaw Pamela , Jenkins Thomas 
Published: August 2022

This study aimed to quantify, characterise and localise motor fatigue in people with motor neuron disease (MND) using a combination of clinical assessments, neurophysiology and muscle phosphorus-31 magnetic resonance spectroscopy (31P-MRS).We quantified fatigability using the fatigue index (FI) in twenty patients and 10 healthy controls. F-wave amplitudes, motor unit number index (MUNIX) and 31P-MRS were acquired pre- and post-maximal voluntary contraction to investigate fatigability at different sites of the motor system (spinal cord, peripheral nerve and muscle, respectively). Between-group differences and associations were assessed using regression models.There were no between-group differences in FI (p=0.115). MUNIX (p=0.008) and f-wave amplitude (p=0.024) declined significantly post-contraction in controls, but not in patients (MUNIX p=0.284, f-wave p=0.264). FI was associated with resting intracellular magnesium (R=0.869, p=0.001, FDR-corrected) in controls, but not patients. Resting magnesium and post-contraction MUNIX decrease were associated with greater fatigue in controls. A decrease in post-contraction f-wave amplitude was associated with greater fatigue in patients, after accounting for denervation (MUNIX) and magnesium.There is a differential response to fatigue in MND compared to healthy controls. Fatigability appears related to spinal excitability (f-waves) in patients, whereas peripheral (MUNIX) and muscular (magnesium) components predominate in healthy controls.
185 JEWELFISH: Safety, pharmacodynamic and exploratory efficacy data in non-naïve patients with SMA receiving risdiplam
Authors: Scoto Mariacristina , Bruno Claudio , Fischer Dirk , Kirschner Janbernd , Mercuri Eugenio , Carruthers Imogen , Gerber Marianne , Kletzl Heidemarie , Warren Francis , Chiriboga Claudia ,   on behalf of the JEWELFISH Working Group
Published: August 2022

Risdiplam (EVRYSDI®) is an oral survival of motor neuron 2 (SMN2) pre-mRNA 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 SMN2 copies.JEWELFISH (NCT03032172) is an open-label study of risdiplam in patients with SMA who previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec (ZOLGENSMA®).JEWELFISH assesses the safety, tolerability and pharmacokinetic/pharmacodynamic (PD) relationship of risdiplam in a broad range of ages (1–60 years), SMA types (1–3), SMN2 copy numbers (1–4) and motor function (nonsitters, sitters and walkers). We previously presented safety data from 173 patients (data cut-off: 31 July 2020): 13 previously received RG7800, 76 received nusinersen, 70 received olesoxime and 14 received onasemnogene abeparvovec. Risdiplam led to a rapid and sustained >2-fold increase in SMN protein (data cut-off: 1 June 2020), consistent with data from treatment-naïve patients with Types 2/3 SMA (SUNFISH;NCT02908685).No drug-related safety findings leading to withdrawal were reported for any patients in JEWELFISH. The safety profile of risdiplam was consistent with observations in treatment-naïve patients. Here we present 12-month safety, PD and exploratory efficacy data.
189 Real world experience on use of rituximab at regional refractory myasthenia gravis clinic in Birmingham
Authors: San Pyae Phyo , Jacob Saiju , Sadalage Girija , Roe Alice 
Published: August 2022

Myasthenia gravis (MG) is a T-cell dependent B-cell mediated autoimmune disease targeting neuro- muscular junction.Rituximab is a chimeric CD20 monoclonal antibody which gives consistently high response rates in anti- Muscle Specific Kinase antibody positive MG. In contrast, the response rates were variable for anti-Ace- tylcholine Receptor antibody positive MG.NHS approved use of rituximab in specific circumstances in Myasthenia patients since 2019. Our NHS regional refractory MG clinic reviewed 15 patients who received Rituximab from 2019 to 2021. 14 were anti-AchR positive and 1 was anti-LRP4 positive. 7 had severe disease (MGFA Class IV/V). 12 had had prednisolone and at least 2 other immunosuppressants.9 received standard Rituximab regime of 2 doses of 1 Gram 2-weeks apart. 6 received more than 2 doses due to unsatisfactory clinical improvement or relapse. From an average of 10% before treatment, periph- eral CD19+ B cell depletion to 0% was achieved in all although 3 had reappearance with one needing retreatment due to an accompanying clinical relapse.OutcomeEfficacy in MGFA Post-Intervention Status: 2 achieved Minimal Manifestations-3, 2 >50% Improved, 5 <50% Improved, 5 Unchanged and 1 Worse.SafetyNone experienced side effects.Further analysis of steroid dose reduction and long-term outcome is currently being undertaken.
191 Real world treatment with risdiplam in adults with type-2 spinal muscular atrophy at St George’s Hospital, London
Authors: Ambawatte Sathyajith Buddhika , Weidner Derek , Chatfield Sherryl , Appleton Pamela , Matthews Emma , Nirmalananthan Niranjanan , Galtrey Clare 
Published: August 2022

Risdiplam is a pre-mRNA splicing modifier designed to treat 5q-SMA. We describe our experience prescrib- ing Risdiplam to adults with type-2 SMA with a wider range of ages and comorbidities than in clinical trials.Risdiplam was prescribed for nine people aged 20 to 56-years; six males. Eight patients had homozygous exon-7 and 8 deletions; one had isolated homozygous exon-7 deletions. Seven patients had three copies of the SMN-2-gene, two had four copies. Seven patients had spinal surgery and two had severe scoliosis. They had between 0-5 comorbidities and 1-12 other drugs already prescribed and were all assessed for known interactions. They had blood tests (month 1, 3, and 6), ECG, and visual function assessment. Females of childbearing age were offered long-acting contraception and males were offered sperm banking.Seven patients required non-invasive ventilation while two had dysphagia (one with gastrostomy). Baseline forced-Vital-Capacity (19%-74%), RUL (score 0-19), CHOP-ATTEND (score 19-46), and 9-hole-peg-test and dynamometer were measured as appropriate.One experienced abdominal pain and increased weakness (Risdiplam was stopped). One patient had transaminitis and treatment was withheld and restarted later at a lower dose and is being gradually increased.We found Risdiplam is generally well tolerated, especially for those with greater disability and spinal surgery.
Associations between antiepileptic use and hypogammaglobulinaemia: findings from a population-based case-control study using data linkage
Authors: Perrott Sarah , Macleod Angus 
Published: August 2022

BackgroundAntiepileptic drugs (AEDs) have been previously associated with transient hypogammaglob- ulinaemia in small case series, which may predispose patients to infections. This study aimed to determine if an association exists between AEDs and hypogammaglobulinaemia.MethodsA case-control study was conducted using data linkage of biochemistry, prescribing and morbidity data from 2009-2021. Cases were participants with immunoglobulin levels less than the normal range. Logistic regression was used to investigate associations between AED exposure and hypogamma- globulinaemia, adjusting for age and sex. Secondary analyses were conducted, investigating outcomes of low IgA, IgM and IgG separately. Cumulative exposure data were used to determine whether a exposure-response relationship exists.Results18,666 cases and 127,157 controls were identified. AEDs were associated with increased risk of hypogammaglobulinaemia (adjusted odds ratio (aOR) 1.26 (95% confidence interval 1.21-1.31), p<0.001). Individual AEDs (except topiramate) were also associated with significantly increased hypogammaglob- ulinaemia risk to varying degrees. There was evidence of an exposure-response relationship for those treated with any AED.ConclusionAEDs may increase hypogammaglobulinaemia risk. Specific classes of immunoglobulins are differentially affected, and risk may increase with AED exposure. Clinicians should test immunoglobulin levels if unusual or recurrent infections occur. Further research should assess whether AED-associated hypogammaglobulinaemia increases infection risk.
An astra-nomical headache
Authors: Mukherjee Trisha , Needham Edward , Crisp Sarah 
Published: August 2022

IntroductionWe present a case of myelin-oligodendrocyte glycoprotein antibody disease (MOGAD) requiring long-term immunosuppression triggered by a dose of the AstraZeneca COVID-19 vaccination. Relapsing MOGAD is thus far an unknown complication of COVID-19 vaccination.Case Description: A 58-year-old lady developed headache, nausea, dizziness, facial numbness, ataxia and slurred speech 8 days after the COVID-19 AstraZeneca vaccination. Her imaging showed acute disseminated encephalomyelitis (ADEM) with a white matter lesion in the left cerebellum and bilateral smaller lesions. Her cerebrospinal fluid showed 38 white cells and elevated protein. She initially responded well to steroids, however relapsed with optic neuritis 7 months later, requiring long-term immunosuppres- sion with mycophenolate mofetil.DiscussionAlthough there have been some case reports of MOGAD following COVID-19 infection, to our knowledge this is only the second reported case of MOGAD following vaccination against COVID-19, and the first such case to require long-term immunosuppression. The other reported case also occurred following the COVID-19 AstraZeneca vaccine, and also presented with ADEM. This is in contrast to reported cases of MOGAD following COVID-19 infection, where adults mostly presented with optic neuritis. We wanted to highlight the possibility of this vaccine-related neurological complication occurring, particularly in the context of potentially frequent ongoing COVID-19 booster vaccinations.
010 Trigeminal neuralgia in diffuse scleroderma – a rare but recognised association
Authors: Talbot Jamie , Patel Rachel , Gormley Joe 
Published: August 2022

Trigeminal neuralgia is a common cause of facial pain, typically producing paroxysmal bursts of shooting pain in one or more divisions of the trigeminal nerve. Whilst it usually occurs as a primary phenomenon due to neurovascular conflict, secondary causes account for around 15% of cases, most commonly cerebellopontine angle tumours. Multiple sclerosis is another common secondary cause of presumed inflammatory aetiology.We report a case of trigeminal neuralgia in association with diffuse scleroderma. A 43 year old carpenter presented with typical symptoms of unilateral facial pain around a year after receiving a diagnosis of systemic sclerosis with seropositivity to Scl-70 and centromere antibodies. MR imaging at the time revealed enhancement of the left trigeminal nerve, which resolved on subsequent imaging six months later.The association of trigeminal neuralgia and diffuse scleroderma has previously been reported, with a recent case-control study providing novel evidence of a direct association between the two conditions. Nevertheless it represents a very rare cause in patients presenting to the neurology clinic. In this presen- tation we explore the subject of secondary trigeminal neuralgia and provide a précis of the up-to-date management for this painful condition.
015 Service evaluation: the role of same day emergency care in managing acute neurological presentations
Authors: Hsu Catherine , Elrhermoul Fatima-Zahra , Maduakor Chinedu , Everitt Alex , Gabriel Carolyn 
Published: August 2022

Background and aimDuring the COVID-19 pandemic, the neurology department at St Mary’s Hospital had to direct the bulk of its acute work to a newly expanded ‘hot clinic’ running Monday to Friday through Same Day Emergency Care (SDEC). Face to face clinic appointments were also halted and instead triaged to SDEC when examination of the patient was necessary. Patients were referred through a number of routes directly to the neurology consultants or on-call registrar, and subsequently seen on an urgent basis. We were interested in evaluating the types of referrals made to this service as well as their final outcomes.ResultsA total of 255 patients were seen between 3 March 2021 and 3 August 2021. Approximately a third were from the A&E department and just less than a third were from the Western Eye Hospital, our local ophthalmology A&E. Most referrals were for headache or visual change, and 61% of patients did not need to re-attend SDEC. Importantly, a quarter were discharged home after specialist review, and none required admission from clinic. Thus our emergency service was successful in avoiding admissions while ensuring patients received the care they required in a timely fashion.
020 The headache hub: a multidisciplinary diagnosis and management resource for GPs
Authors: Logan Anne-Marie , Lee Nicholas , Patel Bhavini , Dolling Rebecca , Pink Katharine , Nitkunan Arani , Mansour Nassif , Khan Usman , Wilkinson Thomas , Nirmalananthan Niranjanan 
Published: August 2022

The need to improve care of patients with headache prompted development of a new model in South West London. The Headache Hub, piloted at St George’s University Hospitals NHS Foundation Trust, consisted of a multidisciplinary team; Consultant Neurologists, GP with Extended Role and Allied Health Professionals. The Hub triages new GP referrals and offers an online migraine group clinic (engaging patients through shared medical appointments in a group setting).Between April-December 2021, 171 GP referred patients were seen, of which 96 (48%) had Chronic Migraine (CM), 36 (18%) High Frequency Episodic Migraine and 23 (12%) Low Frequency Episodic Migraine patients. CM patients reported 31 ED attendances in the prior year and 53% had the highest unmet needs, HURT 8 (Headache Under Response to Treatment) score 17-24. Real-time data on waiting times enabled clini- cians to make informed follow up choices.Triage to “consultant only” occurred in 56% of referrals, enabling a subsequent reduction in consultant caseload to address tertiary headache waiting lists. Patient satisfaction was high (80%) and group clinic feedback highlighted beneficial shared experiences; “super productive and made me feel not so alone in a challenging time”.This model is being considered at other secondary care hospitals in the region.
021 Experience from a SARS-CoV2 neurology clinic at the national hospital of neurology and neurosurgery
Authors: Jacinto Simeona , Berry Alex , Levee Viva , Heightman Melissa , Hillman Toby , Iodice Valeria , Cipolotti Lisa , Manji Hadi , Zandi Michael S , Namara Patricia Mc 
Published: August 2022

IntroductionThe profile of neurological disorders post-SARS-CoV-2 remains unclear. We describe obser- vations from a SARS-CoV-2 neurology clinic established to meet demand.MethodsA retrospective case-note review of consecutive patients attending a SARS-CoV2 neurology clinic over a 6-month period was conducted. Demographics, clinical features, medications and inves- tigation results were collected.ResultsThere were 122 patients included (78 female: 44 male, median age 44 years); all met WHO criteria for probable or confirmed SARS-CoV2 infection and 15.6% were hospitalised. Most frequently reported symptoms included fatigue (82.0%), cognitive disturbance (63.9%) and headache (63.9%). Attentional deficits were the most common observation on formal neuropsychometry and were associated with fatigue, sleep-impairment, migraine and anxiety symptoms (p<0.05). Majority of neuroimaging was reas- suring; only 3 patients had findings attributable to SARS-CoV2. Neurophysiology results were significant in 2 of 25 tests. Autonomic testing revealed vasodepressor syncope or postural tachycardia syndrome in 7 of 16 cases. Median follow-up was 186.5 days (range 25-552) and 59.8% reported improved symptoms.ConclusionThe majority of patients had normal brain imaging and showed improvement. Further research is required to look into the biological mechanisms underlying neurological symptoms in SARS-CoV2 including in those not hospitalised for their initial illness.
Parallel Session 2: Neurodegeneration| Wed 18 May, 1115 – 1230|2 Degraded speech comprehension is a ‘real-world audiogram’ for dementia
Authors: Johnson Jeremy , Jiang Jessica , Benhamou Elia , Requena-Komuro Mai-Carmen , Sivasathiaseelan Harri , Nelson Annabel , Rohrer Jonathon , Bamiou Doris-Eva , Hardy Chris , Warren Jason 
Published: August 2022

UCLThe recently recognised association between hearing impairment and dementia has important clinical and public health implications but remains poorly understood. In daily life, the most important sound we hear is speech: making sense of spoken messages that are ‘degraded’ by noise is fundamental to suc- cessful communication and depends on neural computations in the auditory brain that are vulnerable to neurodegenerative pathologies. Measuring degraded speech perception might therefore index both real-world hearing function and the underlying disease process in dementia.We administered tests of degraded speech and pure tone audiometry, before correlating these measures with questionnaire data on real-world hearing ability in healthy control participants and patients with Alzheimer’s disease (AD), frontotemporal dementia (FTD) and the primary progressive aphasias (PPA). Audiometric performance was modulated by auditory cognitive performance and correlated poorly with real-world hearing ability. Degraded speech tests were able to stratify syndromic groups and showed significantly better correlation with real-world hearing measures.Our findings suggest that auditory brain function is a critical determinant of daily life communication in people with dementia: tests of auditory cognition may constitute a ‘real-word audiogram’ for these diseases, adding value to standard audiometry and potentially detecting neurodegenerative patholo- gies earlier.