bluuebunny/crossref_metadata_2025 huggingface dataset:
106 Critical ischaemia without infarction presenting as progressive hemichorea: a case study and literature review
Authors: Wrigley Sarah , Killeen Ronan , O’Riordan Sean
Published: August 2022

A 69 year old lady with COPD presented with a 3-week history of progressive worsening involuntary movements of her right limbs, beginning in her right hand, and spreading to involve her right leg after 1 week. Three days prior to admission, she had an episode of dysarthria and orolingual numbness lasting five minutes. On examination, she was hypertensive (200/105mmHg), and had marked right hemiballismus/hemichorea, with subtle orolingual chorea. Her neurological and cognitive examination was otherwise normal. The hemichorea worsened with commencement of antihypertensive therapy.

It seemed likely that our patient’s presentation with subacute hemichorea/hemiballismus and a superim- posed recent TIA-like event was due to an ischaemic stroke affecting the left basal ganglia. However, CT and MRI brain imaging did not demonstrate acute ischaemia or a prior stroke of the left basal ganglia. But on further investigation, CT angiogram revealed short segment 95% stenosis of the left internal carotid artery. The patient underwent a left carotid endarterectomy. Six weeks later, there was complete resolu- tion of hemichorea.

The progressive nature of her clinical signs over three weeks, the transient worsening with antihypertensive therapy, and the gradual resolution post-operatively suggests that critical cerebral hypoperfusion due to severe internal carotid artery (ICA) stenosis can present unusually as progressive hemichorea.
110 Outcome and mortality of hospital admission with COVID-19 for individuals with parkinsonian syndromes
Authors: Sorrell Lexy , King Angela , Inches Jemma , Rideout Jane , Sneyd Robert , Kobylecki Christopher , Chaudhuri Ray , Walker Richard , Martin Hannah , Carroll Camille
Published: August 2022

Objective

To evaluate features of Parkinson’s disease (PD) and atypical Parkinson’s syndromes (APS) associated with poor outcome and mortality in people with COVID-19 in a hospital setting.

Background

Previous studies have demonstrated increased mortality of COVID-19 in people with PD. However, it is not known whether this is associated with disease-related factors (eg autonomic dysfunc- tion, dysphagia).

Methods

An online survey tool captured anonymised patient data from hospital admission records of people with PD and APS who tested positive for COVID-19 between February 2020 and July 2021. We will use Cox proportional hazards and linear regression models to evaluate which characteristics are associ- ated with mortality, increased care requirement and more severe COVID-19 infection. Models will be adjusted for known associations with poor outcome, such as co-morbidities, age and sex.

Results

Data were collected from 556 admissions from 21 UK sites: 66.2% male; median (IQR) age 80 (11) years; median disease duration 5 (7) years. 19.2% were asymptomatic, 28.8% had mild symptoms and 52.5% required respiratory support. 38.3% died within 4 weeks of a positive COVID-19 test. Preliminary Kaplan-Meier curves suggest that co-existing dementia, marked motor fluctuations and more advanced Hoehn and Yahr stage may be associated with 28-day mortality. Full statistical analysis is in progress.

Conclusions

Identification of Parkinson’s features associated with poor in-hospital COVID-19 outcome will allow a more informed discussion relating to individual COVID-19 risk.
113 Assessing predictors of NEDA in RRMS patients initiating dimethyl fumarate in a real-world setting
Authors: Al-Araji Sarmad , Bianchi Alessia , Eshaghi Arman , Zhang Le , Kanber Baris , Jha Ashwani , Goodkin Olivia , Barkhof Frederik , Nachev Parashkev , Ciccarelli Olga
Published: August 2022

Introduction

No evidence of disease activity (NEDA) is a treatment goal when using disease modifying therapy for treating relapsing remitting multiple sclerosis (RRMS).1 However, predicting which patients may achieve NEDA is challenging.

Objective

To identify the baseline clinical and MRI features that predict NEDA in patients initiating dimethyl fumarate (DMF).

Method: In our observational study, we retrospectively collected clinical and radiological data acquired for patients with RRMS initiating DMF. Demographics and clinical details at MS onset and at DMF initiation (baseline) were evaluated. We investigated the associations between all the baseline clinical and MRI findings and NEDA at 24 months using a combined multiple logistic regression.

Results

We had a total of 670 patients in our cohort and only 339 (50%) achieved NEDA at 24 months. Lower EDSS (Log odds[95%CI]= -0.19[-0.30 to -0.03], p=0.01), lower number of new MRI lesions at baseline (Log odds[95%CI]= -0.14[-0.32 to -0.04], p=0.01) and lower number of relapses in the previous 12 months (Log odds[95%CI]= -0.39[-0.77 to -0.26], p=0.0001) significantly predicted NEDA at 24 months.

Conclusion

Significant predictors for achieving NEDA were the number of relapses in the previous year, the number of new MRI lesions and the EDSS at DMF initiation. This could be useful in clinical practice to counsel patients regarding their potential response to DMF.
116 Evaluating the introduction of subcutaneous natalizumab to a cohort of patients with multiple sclerosis
Authors: Edwards Marc , Pearson Owen , Ingram Gillian
Published: August 2022

Natalizumab was approved for use in the UK as an intravenous (IV) infusion for rapidly evolving multiple sclerosis in August 2007; with the subcutaneous (SC) formulation available in June 2021. This project aimed to assess changes in patient care in Swansea, since the institution of SC natalizumab, assessing patient satisfaction and unit flow. Anonymous data was collected using a questionnaire completed in December 2021.

Of 78 patients, 64 (82%) had switched to, or started treatment with SC. Average combined infusion and sur- veillance time for IV was 142 minutes, reducing to average 61 minutes for SC. Of 50 SC patients completing questionnaires, 7 reported mild adverse reactions including pain, swelling, nausea and fatigue. 84% of SC patients reported increased convenience and 96% patients were satisfied or very satisfied with switching.

Conclusion

Subcutaneous natalizumab is a well-tolerated alternative to the intravenous infusion. In this cohort of patients, the majority were satisfied with switching, finding the SC injection more convenient, although some patients reported more pain especially when delivered in the arm. A major benefit to patients and staff is reduced delivery time, improving access to valuable infusion space. Monitoring will be reduced further to 15 minutes, once patients have received 6 injections.
119 A novel kinematic tool to assess upper limb dysfunction in multiple sclerosis
Authors: Fernandes Linford , Coats Rachel , Mon-Williams Mark , Ford Helen
Published: August 2022

Introduction

We assessed upper limb function in people with progressive MS (pwPMS) using a novel kinematic 3D motion capture methodology.

Methods

42 pwPMS and 15 healthy controls reached-and-grasped different objects while movement trajectories were captured with a kinematic assessment system. Clinical measures included the nine hole peg test (9HPT), Expanded Disability Status Scale (EDSS), and patient reported outcomes at baseline and six months.

Results

PwPMS had longer reaction and reach times, took longer to pick-up objects and move them between pre-defined positions, and spent more time placing objects, compared to controls. PwPMS had lower peak wrist velocities when reaching for and moving objects. Kinematic assessment demonstrated consistent differences between the mild and severe patients, driven by object grasp dimensions, which weren’t captured by 9HPT. There was no correlation between upper limb performance and EDSS, with wide variation in performance across a narrow EDSS range. There was moderate correlation between kinematic assessment and 9HPT. There was no significant change in most of the kinematic or clinical parameters at six months compared to baseline.

Conclusions

Our study has created and tested a novel upper limb function assessment tool with better sensitivity and behaviour capture than the EDSS and 9HPT. For the first time, we have captured the spa- tiotemporal patterns of hand function impairment in pwPMS.
132 Adverse prognostic factors predicting disease modifying therapies in MS: a real- world cohort
Authors: Cauchi Marija , Harding Katharine , Wynford-Thomas Ray , Pickersgill Trevor , Wardle Mark , Robertson Neil , Tallantyre Emma
Published: August 2022

Background

Multiple sclerosis (MS) demonstrates considerable variability in disease course and prognosis. An improved understanding of factors that predict long-term outcome, particularly early in disease allows for informed, personalised decisions to optimise MS treatment.

Methods

Data was collected on sequential, newly diagnosed patients from a single MS centre from 2016-2018. Demographic, clinical, and radiological features at disease onset were documented and number of adverse prognostic factors (APF) listed for individual patients. Number and type of APF was then correlated with outcome variables including EDSS, time to first relapse and DMT choice to understand influence of these factors on early clinical management decisions.

Results

176 people were diagnosed in Cardiff in the 2-year study period. 2 were excluded due to missing baseline imaging. At the time of diagnosis 60% had 3 or more APFs. A higher number of APFs was associ- ated with the decision to prescribe high- versus moderate-efficacy therapies (OR= 1.34; 95% CI 1.04, 1.73, p=0.02) and males were also more likely to receive high-efficacy DMTs (OR 2.11; 95% CI 1.32-3.36, p=0.002).

Conclusions

These data provide description of the frequency and patterns of APFs at time of MS diagnosis and illustrate their influence on initial therapeutic interventions and short-term outcomes.
Autonomic dysfunction after moderate-severe traumatic brain injury: symptom spectrum and clinical testing outcomes
Authors: Li Lucia , Vichayanrat Ekawat , Giovane Martina del , Lai Helen , Iodice Valeria
Published: August 2022

Background

Survivors of moderate-severe traumatic brain injury (msTBI) frequently experience trouble- some unexplained somatic symptoms, which may be attributable to autonomic dysfunction.

Methods

We conducted two cohort studies. Cohort 1 comprises msTBI patients (with controls) prospec- tively recruited from a regional referral TBI outpatient clinic, in whom we assessed subjective burden of autonomic symptoms using the Composite Autonomic Symptom Score (COMPASS31) questionnaire. Cohort 2 comprises msTBI patients who had clinical autonomic function testing, retrospectively identified from referrals to a national referral autonomics unit.

Results

Cohort 1 comprises 39 msTBI patients (10F:20M, median age 40 years, range 19-76), with median time since injury 19 months (range 6-299), and 44 controls (22F:22M, median age 45, range 25-71). Patients had significantly higher mean scores than controls in the weighted total COMPASS-31 score (p<0.001), and also gastrointestinal, orthostatic and secretomotor subscores (corrected p<0.05). Total COMPASS31 score inversely correlated with subjective rating of general health (p<0.001, rs=-0.84). Cohort 2 comprises 18 msTBI patients (7F:11M, median age 44 years, range 21-64), with median time between injury and testing 57.5 months (range 2-416). Clinical autonomic function testing revealed a broad spectrum of autonomic dysfunction in 13/18 patients.

Discussion

Our results provide evidence for clinically relevant autonomic dysfunction after msTBI, even at the chronic stage. We advocate for routine enquiry about potential autonomic symptoms, and demons- trate the utility of formal autonomic testing in providing diagnoses.
136 NOVA primary results randomised controlled study of natalizumab Q6W versus continued Q4W treatment for MS
Authors: Foley John , Defer Gilles , Ryerson Lana Zhovtis , Cohen Jeffrey , Arnold Douglas , Butzkueven Helmut , Cutter Gary , Giovannoni Gavin , Killestein Joep
Published: August 2022

Background

Natalizumab every-6-week (Q6W) dosing is associated with lower progressive multifocal leukoencephalopathy risk than every-4-week dosing (Q4W) in retrospective analyses. NOVA is the first randomised trial to assess Q6W efficacy.

Objective

Evaluate natalizumab Q6W efficacy in patients previously treated with natalizumab Q4W for

≥12 months compared with continuation of Q4W over 72 weeks.

Methods

NOVA is a randomised, controlled, open-label, rater-blinded phase 3b trial. Included patients were treated with natalizumab Q4W without relapse for ≥12 months. Patients were randomised 1:1 to Q4W (n=248) or Q6W (n=251). The primary endpoint was new/newly enlarging T2 (N/NET2) lesions. Secondary endpoints included clinical and safety outcomes.

Results

Proportions of patients with N/NET2 lesions were low in both arms (Q4W:4.1%; Q6W:4.3%). Differ- ences in mean N/NET2 lesions for Q4W and Q6W (primary estimand: 0.05 vs 0.20 [P=0.0755]; secondary estimand: 0.06 vs 0.31 [P=0.0437]) were driven by two Q6W patients with extreme (≥25) values. Secondary outcomes were similar for Q4W and Q6W.

Conclusions

Overall, NOVA data suggest most patients stable on natalizumab Q4W can switch to Q6W without clinically meaningful loss of efficacy. Support: Biogen. Disclosures on poster.
158 Natalizumab treatment satisfaction in TONiC-MS study: preliminary results from i.v.participants on infusion experience
Authors: James Bethan , Mills Roger , Vonsy Jean , Langdon Dawn , Ando Hikari , Young Carolyn
Published: August 2022

Background

MS patients’ perceptions and treatment satisfaction with natalizumab-i.v., as well as their experiences if they switch from natalizumab i.v. to natalizumab-s.c., are being collected in a prospective, observational study, nested in the Trajectories of Outcome on Neurological Conditions (TONiC-MS) study.

Methods

These are postal questionnaire, interim results of participants’ experiences with natalizumab infusions; no patients had switched to s.c. yet.

Results

56 participants, treated at 19 hospitals, responded by 7 January 2022. Median duration of treatment was 7.66 years; 50% (28) had received natalizumab as their first disease modifying therapy. Infusions occurred monthly for 59% (33) and every 6 weeks for 35.7% (20). Infusions normally took 1-2 hours (89.3%) and 52% (29) reported no post-treatment observation.

42.6% (23/54) normally required ≥2 attempts at cannula insertion, of whom 34.8% (8/23) had experienced an infusion treatment which required more than 5 attempts. Pain at cannula site was experienced by 14.3% (8/56). Worry about successful cannulation was reported by 25% (14/56).

Discussion

This is the first UK real-world study on natalizumab patients’ perceptions. These preliminary results highlight cannulation challenges experienced by some i.v. patients. As some patients switch to s.c., we will assess differences and patient preference between the two formulations.
159 The growing role of the neuropharmacist: helping to deal with staff shortages in other professions
Authors: Mathews Joela , Dorsey-Campbell Rachel
Published: August 2022

Introduction

This audit of existing neuropharmacists shows how the role has grown over the years to help look after tasks suited to their skill set such as governance, introduction of new medication and path-way design, which has helped neurology teams in utilising the skills of each member of the team appropriately.

Aim

To showcase the growing role of the neuropharmacist.

Methods

A survey of existing neuropharmacists about their current roles and duties was undertaken, utilising the network of 50 neuropharmacists across the UK.

Results

The role of the neuropharmacist has grown with subspecialism occurring in areas such as MS, headache, epilepsy and parkinsons disease. Patient facing clinics, leading on governance for the neu- roscience team, introduction of new medication to pathways and taking part in research across the healthcare economy (ie with primary care) are all areas that the neuropharmacist has been involved.

Conclusions

The role of the neuropharmacist is diverse and can be utilised by the neurology team to ensure appropriate skill set are used to deliver the best care to patients. It is hope this work will help teams that do not have a neuropharmacist to develop business cases and redesign patient and disease pathways to include other members of the team.
161 Recurrent painful ophthalmoplegic neuropathy vs oculomotor schwannoma
Authors: Seddigh Arshia , Jacob Saiju
Published: August 2022

A 23-year-old female was admitted to ED two weeks after delivery with severe migrainous headaches and a painful pupil-sparing partial right third nerve palsy presenting as diplopia on upward and lateral gaze and a partial ptosis. This was the third such presentation for her as she was diagnosed with oph- thalmoplegic migraine (OM) since 8 years old. A second episode at the 18 years of age required steroid treatment due to a delayed recovery for few months.

Repeat orbit MRI confirmed slightly grown lesion on the right oculomotor nerve compared scans 4 years apart appearing as a thickened nodular enhancement between the P1 segment and superior cerebel- lar artery. Multiple neuro-oncology and neuro-radiology MDTs confirmed this lesion to be an oculomotor nerve schwannoma. She had to be treated with steroids due to deficits and 2 months later while migrain- ous headache was fully resolved, she was still left with subtle upward and lateral gaze diplopia. She will have surveillance imaging and follow up.

Recurrent Painful Ophthalmoplegic Neuropathy (RPON) is replacing OM and expected to be associated with a resolution of the enhancement. Schwannomas on the other hand are known to be growing during pregnancy and affected by hormonal changes. Transient or recurrent oculomotor nerve deficits may be the primary manifestations of cranial nerve schwannoma and we hypothesise this tumour being the cause of her RPON which must be considered in OM.
168 Traumatic brain injury and sociodemographic factors: a review
Authors: Vidot Micha , Wu Kit , Mitchell James , Nitkunan Arani , Carr Georgina
Published: August 2022

Background

To improve equity of service, in line with the aspirations of public policy across the UK, it is imperative that we understand how sociodemographic factors affect the management and care of traumatic brain injury (TBI).

Aims

To describe the relationship between sociodemographic factors and the epidemiology, clinical factors, diagnosis, treatment, patient experience and outcomes for people with TBI.

Methods

We conducted a focused review of published literature from 2000 to 2021 discussing TBI and each of the patient protected characteristics, as outlined in the Equality Act 2010, with additional factors such as education, employment and socioeconomic status also included.

Results

There is some evidence investigating TBI in regards to age, race, sex and gender. There are gaps in research exploring the relationship between TBI and disability, gender reassignment, marriage and civil partnership, pregnancy, religion, sexual orientation, geographical variation, socioeconomic status, settlement status, education and employment.

Discussion

Whilst there is some data on the incidence of TBI, further research is required to examine the association of certain sociodemographic protected characteristics to aid improvements in patient experience and outcomes.
173 Transcriptional phenotypes of a human stem cell model of Spinal Bulbar Muscular Atrophy (SBMA)
Authors: Devine Helen , Malik Bilal , Tyzack Giulia , Hanna Michael , Greensmith Linda , Patani Rickie
Published: August 2022

Background

Spinal bulbar muscular atrophy is a slowly progressive neurodegenerative disease which affects lower motor neurons (MNs). It is caused by a trinucleotide polyglutamine (CAG) repeat expansion in the androgen receptor (AR) gene but the precise mechanisms of degeneration of the MNs in SBMA are complex and remain poorly understood. There are currently no available treatments for patients.

Objectives

The aim of this study was to develop a human iPSC model of SBMA patient MNs in order to characterise early transcriptomic events in SBMA.

Methods

Human iPSCs were differentiated into spinal MNs using an established, developmentally-rational- ised protocol. Samples were collected at key stages in motor neurogenesis for RNA-sequencing followed by transcriptomic and splicing analysis. Live-cell imaging assays for mitochondrial membrane potential and axonal transport of mitochondria and signal endosomes were performed to validate transcriptomic findings.

Results

Over-representation analysis of differentially expressed genes revealed enrichment of DNA damage response and cell cycle pathways. There were reduced transcripts of genes involved in mito- chondrial pathways with reduced mitochondrial membrane potential and anterograde mitochondrial transport in SBMA on live-cell imaging. Alternative splicing events were common and involved adherens junction and extracellular matrix pathways.

Conclusion

Early transcriptional dysregulation, alternative splicing and mitochondrial dysfunction were seen in SBMA MNs as well as genes linked to defective p53/DNA damage response and the cell cycle.

These cellular phenotypes offer potential targets for future clinical treatments.
Prevention of neurological complications during COVID-19: a retrospective analysis of the ISARIC4C national cohort
Authors: Grundmann Alexander , Hardwick Marc , Wu Chieh-Hsi , Semple Malcolm , Böhning Dankmar , Pett Sarah , Michael Benedict , Thomas Rhys , Galea Ian
Published: August 2022

Neurological complications occur in 4% of patients following acute COVID-19 infection, causing significant morbidity with lasting health economic consequences. However treatment studies to date in COVID-19 have not addressed neurological complications as outcome measures.

We therefore performed a retrospective, non-interventional cohort study using the ISARIC-4C platform, assessing 62,729 hospital inpatients with severe COVID-19 between 31 Jan 2020 and 29 Jun 2021. Treatment with dexamethasone, remdesivir or both was compared to standard of care. The primary outcome was a neurological complication, namely stroke, seizure, meningitis/encephalitis or any other neurological complication, occurring at the point of death, discharge, or resolution of the COVID-19 clinical episode. A propensity scoring methodology was used to balance confounding between treatment groups and between patients with and without neurological complications.

Treatment with dexamethasone, remdesivir or both reduced the incidence of neurological complications from severe COVID-19, with odds ratios of 0.76 (0.69-0.83), 0.68 (0.51-0.90) and 0.64 (0.56 -0.72) respec- tively. Neurological complications were associated with increased length of hospital stay, worse ability to self-care on discharge and increased mortality.

This study is the first to focus on the prevention of neurological complications and strongly supports the continued use of both dexamethasone and remdesivir in severe COVID-19. Our results suggest that the established benefit of dexamethasone on mortality in COVID-19 is not associated with an increased burden of long-term neurological disability.
178 Motor neurone disease and sociodemographic factors: a review
Authors: Vidot Micha , Wu Kit , Mitchell James , Nitkunan Arani , Carr Georgina
Published: August 2022

Background

To improve equity of service, in line with the aspirations of public policy across the UK, it is imperative that we understand how sociodemographic factors affect the management and care of patients with motor neurone disease (MND).

Aims

To describe the relationship between sociodemographic factors and the epidemiology, clinical factors, diagnosis, treatment, patient experience and outcomes for people with MND.

Methods

We conducted a focused review of published literature from 2000 to 2021 looking into MND and each of the patient protected characteristics, as outlined in the Equality Act 2010, with additional factors such as education, socioeconomic status and employment also included.

Results

There is plenty of published literature exploring amyotrophic lateral sclerosis (ALS) and the rela- tionship with age, race, sex and gender.

Minimal published data could be found for disability, gender reassignment, marriage and civil partner- ship, pregnancy and maternity, religion and beliefs, sexual orientation, socioeconomic status, settlement status, education and employment. Additionally, there was a lack of data looking into this for the different types of MND.

Discussion

Research in MND has focused heavily upon ALS. Further research into all patient protected characteristics and the different types of MND is required to improve equity in care and patient outcomes.
187 SUNFISH Part 2: 24-month efficacy of risdiplam compared with external control comparators
Authors: Servais Laurent , Day John W , Mazzone Elena S , Oskoui Maryam , Baranello Giovanni , Gerber Marianne , Martin Carmen , McIver Tammy , Yeung Wai Yin , Mercuri Eugenio
Published: August 2022

Risdiplam (EVRYSDI®) is an oral survival of motor neuron 2 (SMN2) premRNA splicing modifier approved by the EMA and MHRA for the treatment of patients aged ≥2 months, with a clinical diagnosis of Type 1, 2 or 3 spinal muscular atrophy (SMA) or 1–4 copies of SMN2.

SUNFISH (NCT02908685) is a two-part, randomised, placebo-controlled, double-blind study in a broad population of patients aged 2–25 years at enrolment, with Type 2/3 SMA. Part 2 assesses the efficacy and safety of the Part 1-selected dose of risdiplam versus placebo in Type 2 and nonambulant Type 3 SMA. Participants were treated with risdiplam or placebo for 12 months; all participants then received risdiplam until Month 24, when patients were offered the opportunity to enter the open-label extension.

The primary outcome of Part 2 – change from baseline to Month 12 in the 32-item Motor Function Measure total score in patients treated with risdiplam (n=120) versus placebo (n=60) – was met. Here we present analyses to compare 24-month data from the risdiplam arm with an external comparator dataset con- taining data from participants in the NatHis-SMA study (NCT02391831) and the placebo arm of a Phase 2 study of olesoxime in patients with SMA (NCT01302600).
Epilepsy mortality in Wales during COVID-19
Authors: Daniels Helen , Lacey Arron S , Mikadze David , Akbari Ashley , Fonferko-Shadrach Beata , Jolling-Hurst Joe , Rees Mark I , Powell Robert H , Kerr Michael P , Pickrell William Owen
Published: August 2022

Purpose

We aimed to compare mortality rates in people with epilepsy in Wales during the pandemic with pre-pandemic rates.

Methods

We performed a retrospective study using population-scale anonymised health records. We identified deaths in people with epilepsy (DPWE), those with a diagnosis of epilepsy, and deaths associ- ated with epilepsy (DAE), where epilepsy was recorded as a cause of death. We compared death rates in 2020 with average rates in 2015–2019 using Poisson models.

Results

There were 188 DAE and 628 DPWE in Wales in 2020 (death rates: 7.7/100,000/year and 25.7/100,000/year). The average rates for DAE and DPWE from 2015 to 2019 were 5.8/100,000/year and 23.8/100,000/year, respectively. Death rate ratios (2020 compared to 2015–2019) for DAE were 1.34 (95%CI 1.14–1.57, p<0.001) and for DPWE were 1.08 (0.99–1.17, p = 0.09). The death rate ratios for non-COVID deaths (deaths without COVID mentioned on death certificates) for DAE were 1.17 (0.99–1.39, p = 0.06) and for DPWE were 0.96 (0.87–1.05, p = 0.37).

Conclusions

The significant increase in DAE in Wales during 2020 could be explained by the direct effect of COVID-19 infection. Non-COVID-19 deaths have not increased significantly but further work is needed to assess the longer-term impact.
199 Mechanical thrombectomy for acute ischaemic stroke – outcomes from Sheffield
Authors: Moore Sophie , Dyde Richard , Tse George , Nagaraja Sanjoy , Endean Keith , Redgrave Jessica , Lindert Ralf , Harkness Kirsty
Published: August 2022

Introduction

Mechanical thrombectomy is now in routine use for acute ischaemic stroke. This service audit examines outcomes and complications in the Sheffield regional centre.

Methods

Data was collected retrospectively for all patients undergoing mechanical thrombectomy at Sheffield Teaching Hospitals from March 2020 – February 2021 using case notes and digital records. The data was analysed for the whole group (n=33), and for the subgroup of patients (n=8) aged over 80.

Results

33 patients, aged 31-87, underwent mechanical thrombectomy. 88% had successful revasculari- sation (TICI grade 2b/3). 48% had a good functional recovery (modified Rankin scale 0-2).

6 patients had haemorrhagic transformation, though none met the SITSMOST criteria for symptomatic intracerebral haemorrhage secondary to procedure. 6 patients (18%) did not survive to 90 days.

In the group aged over 80, outcomes were significantly worse. In this group the rate of successful revas- cularisation was 63%, and good functional recovery (mRS 0-2) was 13%. 90 day mortality was 38%.

Conclusions

Outcomes from mechanical thrombectomy at Sheffield teaching hospitals are good, with nearly half of patients having a good functional recovery. However, outcomes in the subgroup of patients aged over 80 were significantly poorer, with high complication and mortality rates; this warrants further study.
201 A case report of Collet Sicard syndrome
Authors: Noushad Muhammed Ameen , Bhattacharjee Shakya
Published: August 2022

A 41-year-old man presented with complaints of a left sided headache and difficulty manipulating food in his mouth. Examination revealed signs of lower motor neuron palsies of ix, x, xi, and xii nerves. A CT angiogram showed a left sided ICA dissection and a subsequent MRI head with gadolinium contrast showed dissection with the subsequent hematoma causing compression of the cranial nerves that explained his symptoms and signs.
204 Improving access to cardiac monitoring for acute stroke patients: a quality improvement project
Authors: Scott Nicholas , Curbera Nicolas , McManus Julie
Published: August 2022

Introduction

Atrial fibrillation (AF) is an important modifiable risk factor for ischaemic stroke. Detection of AF following acute stroke presentations can be achieved with early prolonged cardiac monitoring.

Methods

We sought to review access to cardiac monitoring (multi-day ambulatory ECG) for stroke patients at the Royal Alexandra Hospital (RAH), Paisley, UK. We retrospectively reviewed patients admitted to the acute stroke unit at the RAH over 3 months (phase I) and then subsequently (phase II) in the 3 months following the implementation of ‘in-house’ cardiac monitors.

Results

A total of 121 patients were reviewed in phase I and 142 patients in phase II. In phase I, 70 patients had cardiac monitors requested out of which 45 had been done (64.3%). In phase II, 81 cardiac monitors had been requested and 71 (87.7%) had be carried out. Average time from request to cardiac monitor- ing being performed was reduced from 17 days in phase I to 5 days in phase II.

AF detection as a percentage of cardiac monitors carried out was similar between the two phases increasing slightly from 15.6% to 16.9%.

Conclusion

The establishment of ‘in-house’ cardiac monitoring improves access to early cardiac moni- toring for patients.
Clinical relevance and utility of GAD65 antibodies in neurological disease: an eight year cohort study
Authors: Brown Rachel , Thomas-Black Gilbert , Garcia-Moreno Hector , Chapman Miles , Chou Michael , Hart Melanie , Fleszar Zofia , Zandi Michael , Giunti Paola , Lunn Michael P
Published: August 2022

Neurological syndromes associated with glutamic acid decarboxylase (GAD) antibodies provide a challenge in understanding disease pathogenesis, interpreting antibody results, and deciding manage- ment. We retrospectively reviewed 277 patients with positive anti-GAD antibodies (≥ 10 IU/mL) at our centre between 2012-2020. 154 (56%) had one or more neurological disorders including 27 stiff person spectrum disorders (SPSD) (18%), 20 cerebellar ataxia (13%), 18 epilepsy (12%), 18 encephalitis (12%),

12 ‘mixed’ (8%), and 59 other neurological disorders (38%). Co-existing autoimmunity was common; 57 (33%) had diabetes and 46 autoimmune thyroid disease (30%). A wide range of GAD titres was seen, but serum GAD antibody titres were significantly higher in patients with ‘classical’ GAD antibody syndromes than other neurological disorders (p<0.0001) or diabetes only (p<0.0001). In patients with ‘classical’ GAD antibody syndromes, both specific neurological syndrome and the presence of diabetes influenced serum antibody titres; neurological syndrome also affected CSF titres. Patients with SPSD or encephalitis were most likely to receive immunotherapy and the most likely to respond to treatment. Overall, GAD antibody titres were not associated with response to treatment. This is largest GAD-antibody cohort reported and together these data provide key lessons for understanding and interpreting GAD antibody-associated syndromes in clinical practice.
Impact of rituximab regime on time to relapse in aquaporin-4 antibody positive neuromyelitis spectrum disorder
Authors: Nasir Moneeb , Hone Luke , Palace Jacqueline , Tallantyre Emma , Kelly Patricia , Isabel Leite M , Robertson Neil , Bestwick Jonathan , Huda Saif , Dobson Ruth
Published: August 2022

Background

Aquaporin-4 (AQP4) antibody associated neuromyelitis optica spectrum disorder (NMOSD) requires long-term immunomodulation. In refractory cases rituximab can be used, however the optimal regime is not established.

Methods

We retrospectively examined different rituximab regimes in AQP4-NMOSD. Standard mono- therapy (SM; 6 monthly infusions), SM plus oral steroids (SM+S), extended interval dosing (EID; with retreat- ment at CD19 >1%) and EID with oral steroids (EID+S) were compared. The primary outcome was time to first clinical relapse. Potential confounders including age, gender, number of previous relapses, and onset phenotype were included.

Results

77 patients were included: 67 females, mean age 34.6, median DSS at rituximab initiation 5.0. 40 were on SM+S, 19 on SM, 8 on EID, and 10 on EID+S, with mean follow-up 38.5 months. 25/77 patients relapsed on rituximab. Median time to first relapse was 39 months (SM+S), 46 months (SM), 54 months (EID) and 42 months (EID+S). Adjusted Cox proportional hazard model revealed no significant difference between rituximab regimes (SM+S as reference; hazard ratio for SM 1.39, 95%CI 0.49–4.1, p=0.55; hazard ratio for EID 0.70, 95%CI 0.15–3.3, p=0.65; hazard ratio for EID+S 1.63, 95%CI 0.48–5.5, p=0.43). 9 significant infections were recorded, 3 in the SM group and 6 in SM+S.

Conclusions

This provides initial evidence that EID could be used for long term treatment of NMOSD. This may improve patient experience and consolidate use of hospital resources.
The Scottish Epilepsy Deaths Study Score (SEDS Score): a risk prediction model for epilepsy-related deaths
Authors: Mbizvo Gashirai , Schnier Christian , Simpson Colin , Chin Richard , Duncan Susan
Published: August 2022

Purpose

Develop a risk prediction model for epilepsy-related death.

Methods

In this age/sex-matched case-control study, we compared adults (aged ≥16 years) suffering epilepsy-related death between 2009-2016 to living adults with epilepsy in Scotland. Cases were captured from national mortality records, and controls from a research database or epilepsy clinics. Medical record data were used in univariable and multivariable conditional logistic regression to develop a risk predic- tion model consisting of four variables chosen a priori. A sum of the factors present was taken to create a risk index – the SEDS Score. Odds ratios (OR) with 95% CIs were estimated.

Results

224 cases and 224 controls were compared (mean age 48 years). Univariables predicting epi- lepsy-related death were recent epilepsy-related A&E attendance (OR 5.1, CI 3.2–8.3), living in deprived areas (OR 2.5, CI 1.6–4.0), developmental epilepsy (OR 3.1, CI 1.7–5.7), alcohol abuse (OR 4.4, CI 2.2–9.2), absent recent neurology review (OR 3.8, CI 2.4–6.1), generalised epilepsy (OR 1.9, CI 1.2–3.0), and mental health problems (OR 1.6, CI 1.0–2.6). SEDS Score model variables consisted of the first three listed above, alongside the number of comorbidities (adjusting variable). Compared to having a SEDS Score of 0, those with a SEDS Score of 1, 2, and 3, had 3.6x (CI 1.9–6.8), 17.2x (CI 7.4–39.6), and 19.8x (CI 5.1–76.6) increased odds of death, respectively.

Conclusion

SEDS Scoring may help predict epilepsy-related death and requires external validation.
003 A case of SARS-CoV-2 Omicron variant associated acute encephalomyelitis
Authors: Dsouza Michelle , Lichtblau Nicole , Siddiqui Sarah , Harikrishnan Sreedharan , Abukhayzaran Nidal , Moses Samuel , Lauckaite Kristina
Published: August 2022

With the ongoing pandemic of SARS-CoV-2 many neurological complications in relation to COVID-19 infection as well as immune-mediated and vaccine-associated phenomena have been described. To our knowledge, there has been no publication of a case of SARS-CoV-2 Omicron variant associated acute encephalomyelitis.

We present a case of a 73-year-old woman with no relevant background history who is otherwise fit and well and fully vaccinated. She suffered from mild COVID symptoms and had a positive PCR test with presumptive Omicron variant on day 2. Five days into her respiratory illness she developed in quick suc- cession sensory disturbances of hands and feet, bilateral asymmetric flaccid leg weakness, and mild arm weakness. She had absent deep tendon reflexes in the legs and diminished deep tendon reflexes in the right arm. MRI of brain and spine showed signal changes in the brainstem, cervical and low thoracic cord in keeping with acute encephalomyelitis. Her CSF showed an inflammatory picture with raised protein of 1.27g/L and no cells. At the time of abstract submission, the patient received treatment with five days of intravenous steroids followed by ongoing plasma exchange and no comment on treatment response can be made at this stage.
005 A case of xanthomatous hypophysitis presenting as recurrent pituitary adenoma
Authors: Nazeer Kabir Khan , Jacob Saiju
Published: August 2022

Xanthomatous hypophysitis is a rare inflammatory disorder of the pituitary gland which can present as a recurrent pituitary adenoma.

We present a case of 58 year old lady initially presented over two decades ago with symptoms of pan- hypopituitarism with extreme lethargy. She has a background history of bacterial meningitis aged 30. MRI brain for the hypopituitarism showed a pituitary adenoma. As she had deterioration in the visual acuity a resection surgery of the presumed pituitary adenoma was done which improved her vision. Histopathology, however did not show features of adenoma but showed cellular infiltrates representing macrophages, admixed with small amount of plasma cells and foamy histocytes, a few B-cells and small number of IgG4 cells. The IgG4-cells were insufficient to make a diagnosis of IgG4 disease.

Over the next year, her vision deteriorated requiring a re-do pituitary debridement again showing foamy macrophages and necrosis with a positive CD68 immunohistochemistry this raised a possibility of xan- thomatous hypophysitis or necrotising hypophysitis.

She had further visual deterioration over the next 6 months for which she was given a course of IVMP which improved her vision significantly without a need for surgery. A follow up MRI with contrast showed reduction in the size of the lesion with no relapse.
008 Is primary new daily persistent headache de novo chronic migraine and chronic tension-type headache?
Authors: Cheema Sanjay , Stubberud Anker , Rantell Khadija , Nachev Parashkev , Tronvik Erling , Matharu Manjit
Published: August 2022

Objective

To compare the clinical characteristics and treatment responses of primary new daily persis- tent headache (NDPH) to transformed chronic daily headache (T-CDH, encompassing chronic migraine and chronic tension-type headache).

Methods

Analysis of prospectively collected clinical data in consecutive patients seen in a headache clinic between 2007 and 2019.

Results

Inclusion criteria were met by 366 patients with NDPH and 696 with T-CDH. There was a lower female preponderance in NDPH than T-CDH (62.6% vs. 73.3%, p <0.001).

Nausea, vomiting, photophobia, phonophobia, motion sensitivity, vertigo, and cranial autonomic symptoms were all less common in NDPH than T-CDH (all p<0.001). Most T-CDH patients (85%) met ICHD-3 criteria for chronic migraine, whereas fewer NDPH patients did (64%).

Acute treatments were less effective in NDPH, and medication overuse was less common (16% vs. 42%, p<0.001). Response to most classes of oral preventive treatments was poor. The most effective treatment in NDPH was doselupin in 45.7% patients (95% CI 34.8-56.5%). OnabotulinumtoxinA was less likely to be effective in NDPH than T-CDH (34% vs. 49%, p=0.003).

Conclusions

Whilst there is overlap in the phenotype and response to treatment of NDPH and T-CDH; NDPH appears to be less symptomatically diverse, and less responsive to treatment.
052 SKYLINE study design efficacy and safety of gantenerumab in participants at-risk for Alzheimer’s disease
Authors: Bullain Szofia , Delmar Paul , Sperling Reisa , Reiman Eric M , Aisen Paul , Wojtowicz Jakub , Bittner Tobias , Ashford Elizabeth , Doody Rachelle S , Ostrowitzki Susanne
Published: August 2022

The anti-amyloid beta (Aβ) monoclonal antibody gantenerumab is in late-phase clinical development for early (prodromal-to-mild) Alzheimer’s disease (AD). SKYLINE is an upcoming Phase III multicentre, ran- domised, parallel-group, double-blind, placebo-controlled secondary prevention study, evaluating the efficacy and safety of subcutaneous gantenerumab in participants at risk for, or in the earliest stages of, AD.

SKYLINE will enrol ~1,200 cognitively unimpaired participants, aged 60–80, with confirmed Aβ pathology (cerebrospinal fluid or positron emission tomography).

Participants will be randomised 1:1 to 211 weeks’ subcutaneous gantenerumab (titrated to 1,020 mg monthly dosage) or placebo treatment administered weekly or every other week. Any participant confirmed as progressing to mild cognitive impairment or AD dementia during the study will undergo a blinded post-progression dose escalation, during which participants on placebo switch to gantenerumab. All parties will remain blinded to the assigned treatment at randomisation.

The primary endpoint is change from baseline to Year 4 in the Preclinical Alzheimer’s Cognitive Composite-5 score. Secondary and exploratory objectives include further efficacy assessments (e.g. clinical progression); safety; pharmacodynamic biomarkers; pharmacokinetics; and identification of additional biomarkers.

SKYLINE will be the first secondary prevention study of subcutaneous gantenerumab in cognitively unim- paired participants at risk for, or in the earliest stages of, AD.
Real-world bleeding in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) and prescribed different combinations of dual antiplatelet therapy (DAPT) in England: a population-based cohort study emulating a ‘target trial’
Authors: Pufulete Maria , Harris Jessica , Pouwels Koen , Reeves Barney C , Lasserson Daniel , Loke Yoon K , Mumford Andrew , Mahadevan Kalaivani , Johnson Thomas W
Published: August 2022

Objective

To estimate the incidence and HRs for bleeding for different dual antiplatelet therapies (DAPT) in a real-world population with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in England.

Design

A retrospective, population-based cohort study emulating a target randomised controlled trial (tRCT).

Data sources

Linked Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES).

Setting

Primary and secondary care.

Participants

Patients ≥18 years old with ACS undergoing emergency PCI.

Interventions

Aspirin and clopidogrel (AC, reference) versus aspirin and prasugrel (AP) or aspirin and ticagrelor (AT); AP evaluated only in patients with ST-elevation myocardial infarction (STEMI).

Main outcome measures

Primary: any bleeding up to 12 months after the index event (HES- or CPRD- recorded). Secondary: HES-recorded bleeding, CPRD-recorded bleeding, all-cause and cardiovascular mortality, mortality from bleeding, myocardial infarction, stroke, additional coronary intervention and major adverse cardiovascular and cerebrovascular events (MACCE).

Results

In ACS, the rates of any bleeding for AC and AT were 89 per 1000 person years and 134 per 1000 person years, respectively. In STEMI, rates for AC, AP and AT were 93 per 1000 person years, 138 per 1000 person years and 143 per 100 person years, respectively. In ACS, compared with AC, AT increased the hazard of any bleeding (HR: 1.47, 95% CI 1.19 to 1.82) but did not reduce MACCE (HR: 1.06, 95% CI 0.89 to 1.27). In STEMI, compared with AC, AP and AT increased the hazard of any bleeding (HR: 1.77, 95% CI 1.21 to 2.59 and HR: 1.50, 95% CI 1.10 to 2.05, respectively) but did not reduce MACCE (HR: 1.10, 95% CI 0.80 to 1.51 and HR: 1.21, 95% CI 0.94 to 1.51, respectively). Non-adherence to the prescribed DAPT regimen was 28% in AC (29% in STEMI only), 31% in AP (STEMI only) and 33% in AT (32% in STEMI only).

Conclusions

In a real-world population with ACS, DAPT with ticagrelor or prasugrel are associated with increased bleeding compared with DAPT with clopidogrel.

Trial registration number

ISRCTN76607611.
Individualised left anterior oblique projection for lead implantation into interventricular septum
Authors: Narumi Taro , Naruse Yoshihisa , Kaneko Yutaro , Sakakibara Tomoaki , Sano Makoto , Mogi Satoshi , Suwa Kenichiro , Ohtani Hayato , Urushida Tsuyoshi , Saotome Masao , Maekawa Yuichiro
Published: August 2022

Objective

We sought to investigate whether it is possible to obtain individualised left anterior oblique (LAO) by preprocedural electrocardiographic parameters and, if so, whether these parameters can help to improve the success rate of right ventricular (RV) lead implantation into the interventricular septum.

Methods

In this observational study, we assessed the relationship between preoperative electrocardiographic parameters and the angle of the interventricular septum obtained using thoracic CT. The participants were divided into two groups: a retrospective derivation cohort to derive the optimal formula for the individual septum axis, and a prospective internal validation cohort to which we applied the optimal formula and implanted using the new method.

Results

In the retrospective derivation cohort (n=39), the mean angle of individualised LAO assessed by thoracic CT was 53.1°±8.9°, and the preoperative ECG QRS axis was strongly correlated with the interventricular septum axis (R2=0.490). LAO projection derived from the preoperative ECG QRS axis confirmed that the RV lead was placed in the interventricular septum during the pacemaker procedure in the prospective internal validation group (n=30). The success rate for placing the RV lead into the interventricular septum was significantly improved in the internal validation cohort (93% vs 64%, p<0.05). In addition, the N-terminal pro-brain natriuretic peptide level decreased significantly after surgery in the interventricular septal indwelling group.

Conclusions

Individualised LAO angle derived from the preoperative ECG QRS axis is a new useful and simple method for RV lead implantation into the interventricular septum.

Trial registration number

UMIN000045741.