bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality: systematic review and meta-analysis
Authors: Talic Stella , Shah Shivangi , Wild Holly , Gasevic Danijela , Maharaj Ashika , Ademi Zanfina , Li Xue , Xu Wei , Mesa-Eguiagaray Ines , Rostron Jasmin , Theodoratou Evropi , Zhang Xiaomeng , Motee Ashmika , Liew Danny , Ilic Dragan
Published: August 2022

Objective

To review the evidence on the effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality.

Design

Systematic review and meta-analysis.

Data sources

Medline, Embase, CINAHL, Biosis, Joanna Briggs, Global Health, and World Health Organization COVID-19 database (preprints).

Eligibility criteria for study selection

Observational and interventional studies that assessed the effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality.

Main outcome measures

The main outcome measure was incidence of covid-19. Secondary outcomes included SARS-CoV-2 transmission and covid-19 mortality.

Data synthesis

DerSimonian Laird random effects meta-analysis was performed to investigate the effect of mask wearing, handwashing, and physical distancing measures on incidence of covid-19. Pooled effect estimates with corresponding 95% confidence intervals were computed, and heterogeneity among studies was assessed using Cochran’s Q test and the I2 metrics, with two tailed P values.

Results

72 studies met the inclusion criteria, of which 35 evaluated individual public health measures and 37 assessed multiple public health measures as a “package of interventions.” Eight of 35 studies were included in the meta-analysis, which indicated a reduction in incidence of covid-19 associated with handwashing (relative risk 0.47, 95% confidence interval 0.19 to 1.12, I2=12%), mask wearing (0.47, 0.29 to 0.75, I2=84%), and physical distancing (0.75, 0.59 to 0.95, I2=87%). Owing to heterogeneity of the studies, meta-analysis was not possible for the outcomes of quarantine and isolation, universal lockdowns, and closures of borders, schools, and workplaces. The effects of these interventions were synthesised descriptively.

Conclusions

This systematic review and meta-analysis suggests that several personal protective and social measures, including handwashing, mask wearing, and physical distancing are associated with reductions in the incidence covid-19. Public health efforts to implement public health measures should consider community health and sociocultural needs, and future research is needed to better understand the effectiveness of public health measures in the context of covid-19 vaccination.

Systematic review registration

PROSPERO CRD42020178692.
Through the eyes of hospital-based healthcare professionals: exploring their lived experience during the COVID-19 pandemic
Authors: Mathura Pamela , Li Miriam , Vegt Jennie , Penrod Zoe , Suranyi Yvonne , Osborne Cathy , Kassam Narmin
Published: August 2022

Objective

The spread of the COVID-19 virus has caused an unforeseen strain on the healthcare system and particularly on healthcare workers (HCW). In this study, 1 year after the COVID-19 pandemic began, we used photovoice, a visual photographic approach, to understand HCW needs, concerns and resilience and to determine improvement strategies aligned with the HCW-described challenges.

Methods

Using a qualitative design, HCW were recruited from a single Western Canadian hospital, voluntarily submitting a photographic image and narrative that depicts their experiences. An artist artistically enhanced the photovoice submissions, which were then displayed at the hospital-based art gallery for public display. A survey was used to collect feedback from gallery viewers. Inductive thematic analysis was completed identifying themes from the photovoice narratives and survey comments, aiding the identification of recommendations.

Results

There were 25 submissions, and 1281 individuals viewed the art exhibit. Six themes emerged: (1) hopeful and resilient, (2) pandemic fatigue-negative mental and physical states, (3) personal protective equipment is our armour but masks who we are, (4) human connection, (5) responsibility, preparation and obligation and (6) technology surge. According to survey results from the art exhibit, the use of photovoice was a creative method that personalised the HCW experience and validated viewers’ perceptions of the difficulties faced by HCW. Ten improvement strategies that were aligned with the described challenges were identified.

Conclusion

The ongoing COVID-19 pandemic continues to strain HCW. Photovoice has great potential in the professional clinical setting to provide unique insights that narrative language alone cannot capture. Future research exploring the longitudinal impact of COVID-19, reviewing photographs at different timepoints could be beneficial. Using this method as a creative outlet intervention and evaluating participation artistic experience may offer additional insights to further support both HCW and patients.
068 Effect of low dose adjunctive perampanel in adults and adolescents with focal- onset seizures
Authors: Giallonardo Anna Teresa , Aguglia Umberto , Goldman Samantha , Chiacchiaretta Martina , Gentile Anna , Patten Anna
Published: August 2022

Background

We report a post hoc analysis of the efficacy and safety of low dose adjunctive perampanel 4 mg/day in adults and adolescents from A Mirroring Clinical Practice Study in Italy (AMPA;NCT04257604).

Methods

AMPA was a prospective, observational study in patients aged ≥12 years with focal-onset seizures (FOS). Patients were prescribed adjunctive perampanel per the approved indication. Seizure diaries and treatment-emergent adverse events (TEAEs) were verified at baseline and study visits. The primary endpoint was change from baseline in seizure frequency/28 days at Month 6. Secondary endpoints included: 50% and 75% responder rates, seizure-freedom rates, retention rates and safety (≤12 months).

Results

Of the 234 patients who received adjunctive perampanel, 62 (26.5%) received a modal peram- panel dose of 4 mg/day and were included in the Safety Analysis Set. The 6-month median reduction from baseline in all-seizure frequency was 55.4% (95% confidence interval, 31.7%-90.3%). The 12-month 50% and 75% responder, seizure-freedom and retention rates were 57.1%, 46.9%, 26.0% and 46.8%, respec- tively. TEAEs occurred in 50% of patients; the most common TEAE was dizziness/vertigo (17.7% [n=11]).

Conclusions

Adjunctive perampanel at 4 mg/day is efficacious and safe in adult and adolescent patients with FOS in a real-world clinical setting. Funding: Eisai s.r.l.
073 Fenfluramine exhibits disease-modifying effects in a mouse model of Dravet syndrome
Authors: Reeder Thaddeus , Cha John , Filatov Gregory , Smith Steve , Wong Darren , Gammaitoni Arnold
Published: August 2022

Rationale

Fenfluramine (FFA) provides clinically significant reductions in convulsive seizure frequency and improved executive function in patients with Dravet syndrome (DS). FFA also reduces sudden unexpected death in epilepsy (SUDEP) in mouse models of DS. We investigated FFA effects upon survival, myelination, and neuroinflammation in a mouse model of DS.

Methodsscn1a+/-mice (DS mice) were treated subcutaneously with FFA. FFPE sagittal brain sections were immunostained with D-MBP antibody for degenerated myelin and CD11b antibody for inflamma- tory microglia.

Results

In animals receiving FFA, the mortality rate was reduced to 24% (P< 0.01; Figure 1). Degenerated myelin was enriched in DS mouse cortex and hippocampus compared to wild-type controls. FFA treatment reduced degenerated myelin.

Conclusion

This is the first report of increased survival and reductions in myelin degeneration and neuro- inflammation in DS mice treated with FFA. Improved survival and reduced myelin damage and neuroin- flammation demonstrates the claim that FFA exhibits disease-modifying effects in animal models of DS.
088 Croydon neurology assessing the use of a new headache pathway and referral form
Authors: Elsherif Lamiaa , Nitkunan Arani
Published: August 2022

A headache pathway and referral form was implemented across Southwest London in September 2020 – it includes prompts about migraine preventer use. This study aimed to assess its use at Croydon University Hospital.

From 07/04/2021 to 05/08/2021, data were extracted retrospectively from referral and clinic letters for neurology outpatients (first appointments only) given a diagnostic code of a primary headache disorder; including the number of ED attendances in the year before and 3-6 months after their appointment. Appropriateness was determined against the recommendations in the pathway.

Primary headaches accounted for 153 (8%) first appointments compared to 13% in 2016. 73% were dis- charged. 26% of referrals used the referral form with 37% being appropriate. The main reasons for referral were seeking advice (35%) and uncertain diagnosis (33%). 42 had at least 1 Croydon ED attendance in the year before their appointment reducing to 6 in the 3-6 months afterward.

Despite this pathway coming into use during the pandemic, a quarter of referrals exercised the form. As it embeds and with the use of Advice and Guidance and teaching, we hope to enable more GPs to be confident in managing these patients.
095 Artificial Intelligence based detection of Parkinson’s disease in magnetic resonance imaging brain scans
Authors: Courtman Megan , Thurston Mark , McGavin Lucy , Caroll Camille , Sun Lingfen , Ifeachor Emmanuel , Mullin Stephen
Published: August 2022

Background

There is a need for diagnostic tests of early PD diagnosis. A subset of AI known as deep learning (DL) has shown great promise in diagnostic medical imaging, sometimes outperforming radiolo- gists by detecting patterns invisible to the human eye. Using DL, we explored whether such changes are detectable on routine PD MRI scans.

Methods

We trained a convolutional neural network to classify 138 PD and 60 control brain MRI images acquired from the Parkinson’s Progression Marker Initiative (PPMI) database. Models were assessed using k-fold cross-validation. We used Deep SHapley Additive exPlanations (DeepSHAP) to visualise the contri- bution of individual pixels to the model’s prediction.

Results

A combined dataset of axial T2 and proton density MRI images was classified with 79% accuracy and an area under the curve (AUC) of 0.86. Respectively T2 and proton density models classified cases with 81/84% accuracy and AUC of 0.83/0.88. DeepSHAP heat maps demonstrated predominant interest in midbrain slices.

Conclusion

Our models exhibited good diagnostic performance and demonstrated interest in PD relevant brain regions. We will validate this model in a large dataset of routinely collected NHS MRI scans, many of which predate onset of motor symptoms.
096 Motor and non-motor features of prodromal Parkinson’s in idiopathic anosmia
Authors: Rees Richard , Philpot Carl , Gane Simon , McLelland Lisha , Gill Aneet , Giovannoni Gavin , Simonet Cris- tina , Lees Andrew , Noyce Alastair , Schrag Anette
Published: August 2022

Introduction

Anosmia is common at the point of diagnosis of Parkinson’s disease (PD) and often predates motor symptoms. Other non-motor symptoms are also recognised to predate overt motor impairment in PD.

Objective

To identify prodromal markers of PD in patients with idiopathic anosmia (IA).

Methods

Patients age >55y diagnosed with IA in sub-specialist ENT clinics were recruited to the PREDICT-PD study. We compared them with lower-risk healthy older adults (HA) in PREDICT-PD and PD patients. Par- ticipants were assessed with MDS-UPDRS I-III, as well as standardised assessments of cognition, autonomic function, pain and sleep. The IA group were split into those with mild motor impairment (IA-MMI) and normal motor function (IA-NM), and the comparisons repeated.

Results

We recruited 28 HA, 42 IA and 21 PD. The groups were well matched for age and gender. Compared with HA, IA had worse sleep (PD Sleep Scale p=0.023), depressive symptoms (HADS p=0.03) and gastrointestinal (GI) symptoms (SCOPA-AUT GI p=0.035). 23.8% of IA and 15.0% HA scored >6 on the MDS-UPDRS III (p=0.29). IA-NM did not differ from IA-MMI in any domain, including functional motor tasks.

Conclusion

Participants with IA did not have demonstrable impairments in motor or non-motor tests when compared to healthy older adults, with the exception of sleep, mood and GI symptoms.
100 Antiphospholipid-related chorea
Authors: Farag Mena , Hunt Beverley , Andrews Thomasin
Published: August 2022

Chorea of subacute onset is a movement disorder that typically has a monophasic course. Chorea can be associated with autoimmune diseases such as antiphospholipid syndrome and has been associated with the isolated presence of antiphospholipid antibodies (aPL). Here, we report a patient with isolated aPL-related chorea that unusually followed a relapsing-remitting course.

A female in her forties developed chorea gravidarum during her first pregnancy, eight years previously, and again during her second pregnancy five years ago. Investigations showed high titre triple positivity of aPL. No basal ganglia lesion or signal change was identified on MRI brain. There was no history of arterial or venous thromboembolism or pregnancy morbidity. Her symptoms continued post-partum and she received treatment with low-molecular-weight-heparin, prednisolone and intravenous immunoglobulin, while breastfeeding. Tetrabenazine was trialled, which helped to suppress chorea, though lowered her mood. The chorea remitted. She developed a recurrence of chorea three years later, when she was not pregnant or taking hormone therapy. She had significant irritability. Olanzapine was trialled with benefit and her movements and mood improved. She relapsed with a fourth recurrence of chorea two years later and recommenced olanzapine, with no symptomatic benefit. She is currently trialling pulsed oral methylprednisolone followed by azathioprine.
103 A novel MRI biomarker for ataxia-telangiectasia: evaluating the lack of hypoin- tensity of the dentate nuclei
Authors: Tiet May Yung , Scoffings Daniel , Blanchard Caroline , Dineen Robert , Rita Horvath , Hensiek Anke
Published: August 2022

Background

Ataxia-Telangiectasia (AT) is a rare autosomal recessive multisystemic disorder. Classic AT has a characteristic neurological phenotype but variant AT has a variable presentation leading to diagnostic delay. Early diagnosis is essential for cancer surveillance and but imaging biomarkers are currently lacking.

The lack of hypointensity of the dentate nuclei (DN) in some inherited ataxias has been reported. We evaluate the DN hypointensity in our UK AT cohort.

Methods

26 patients (age range 4-55 years) underwent MRI susceptibility-weight imaging (SWI) across two study sites (the National Paediatric and Adult AT clinics, UK). For the paediatric patients, 14 age-matched controls (age range 5-17 years) also underwent MRI SWI. Evaluation of hypodensity of the DN was made using a visual rating score by two independent investigators for each study site.

Results

The average DN visual rating score for patients 0.55 in paediatric cases (4-17 years, N = 11) and 0.64 in age- and sex-matched controls. In adults (18-55 years, N = 14), the average visual ranking score was 0.07.

Conclusions

We demonstrate failure of hypointensity in the DN in AT patients. We propose that lack of hypointensity in the dentate nuclei is a useful biomarker for AT and easily applicable for clinical practice.
104 Examining the sex differences in the prevalence and incidence of Parkinson disease
Authors: Zirra Alexandra , Rao Shilpa , Bestwick Jonathan , Rajalingam Rajasumi , Marras Connie , Blau-Wendraat Cornelis , Mata Ignacio , Noyce Alastair
Published: August 2022

Background

Parkinson disease (PD) is a major cause of disability affecting >6 million people worldwide. The incidence/prevalence of PD is generally higher in males than females. It is unclear whether male predominance is observed in low- and middle-income countries, where the fastest apparent rate of increase of PD has been observed.

Methods

We searched MEDLINE, SCOPUS and OVID for articles published between 2014-2021 for incidence of PD, 2011-2021 for prevalence, and updated previously published systematic reviews for which the last date of inclusion had been 2014 and 2011. We included 32 articles for prevalence and 30 for incidence. We calculated male/female (M/F) prevalence and incidence ratios, and investigated heterogeneity in estimates.

Results

The combined M/F prevalence ratio was 1.18 (95% CI 1.03-1.36) and incidence ratio was

1.37 (95% CI 1.22-1.53), lowest in Asian populations. These were not influenced by study type, national economy or mean participant age. The female-to-male gap in life expectancy did partly account for data heterogeneity.

Conclusion

The sex gap for prevalence of PD was smaller than has previously been reported. More studies are needed to understand the determinants of sex imbalance in PD.
108 An analysis of specialist services for Huntington’s disease in the UK
Authors: Blair Rachel , Haw Alistair , Rickards Hugh , Rosser Anne , Stanley Cath , Willcock Rosa , Hossain Pushpa , Rodríguez-Santana Idaira
Published: August 2022

Introduction

Huntington’s disease (HD) services throughout the UK have grown organically and are embedded in different healthcare specialties: psychiatry, neurology and genetics. There is currently no picture of how these services are delivered nationally. This project was undertaken to map the current organisation, resources and funding of HD services and explore future resource needs.

Methods

This was a mixed methodology study. Existing HD services were identified using desktop research and data was collected on each service via a cross-sectional online survey and follow-up web-assisted semi-structured interviews led by the HDA or SHA.

Results

31 specialist HD services were identified: 18 in England, 10 in Scotland, 2 in Wales, and 1 in N Ireland. The survey included 27 out of 31 (four centres did not respond). Over half of specialist services were led by a mental health trust (n=7) or tertiary referral hospital (n=7), and the majority had a neurologist (n=10) or psychiatrist (n=8) as clinical lead.

The mean number of patients managed by each service was 173, ranging from 5 to 950. On average 18% were pre-manifest, 24% stage 1-2, 32% stage 3 and 26% stage 4-5.

This project is funded solely by Roche Products Ltd.
115 Treatment of non-HIV progressive multifocal leukoencephalopathy with pem- brolizumab: a single-centre case series
Authors: Jacobs Carmen , Cox Thomas , Colchester Nancy , Morris Rhiannon , Lovett Joanna
Published: August 2022

Progressive multifocal leukoencephalopathy is a rare condition caused by the polyomavirus JC (JCV) affecting almost exclusively immunosuppressed individuals. Treatment strategies are limited and generally focus on immune reconstitution. Inhibition of Programmed cell death protein 1 (PD-1) has been associated with reduced CSF JC viral load and clinical stabilisation or improvement in 5 of 8 patients reported in a previous case series (Cortese et al., 2019)[i]. Here, we report three cases of PML in patients without HIV or immunosuppressive treatment who were treated with the checkpoint inhibitor pembrolizumab in an attempt to increase CD4+ and CD8+ T-cell activity against JCV. At time of submission, disease progression had halted in 2 of 3 patients (median follow-up=10months, 1-22months). We will detail presentation and disease course and discuss challenges experienced in the management of these patients.

[i] Cortese I, Muranski P, Enose-Akahata Y, Ha SK, Smith B, Monaco M, Ryschkewitsch C, Major EO, Ohayon J, Schindler MK, Beck E, Reoma LB, Jacobson S, Reich DS, Nath A. Pembrolizumab Treatment for Pro- gressive Multifocal Leukoencephalopathy. N Engl J Med. 2019 Apr 25;380(17):1597-1605. doi: 10.1056/NEJMoa1815039. Epub 2019 Apr 10. PMID: 30969503.
Parallel Session 3: Acute/Vascular/Trauma| Wed 18 May, 1445 – 1600|4 Circulating Interleukin-6 predicts carotid study
Authors: Kamtchum-Tatuene Joseph , Saba Luca , Heldner Mirjam , Poorthuis Michiel HF , Borst Gert de , Rundek Tatjana , Kakkos Stavros , Chaturvedi Seemant , Topakian Raffi ,   et al
Published: August 2022

Background and Aims

Interleukin-6 (IL-6) has important roles in atherosclerosis pathophysiology. To determine if anti-IL-6 therapy could be an adjuvant stroke prevention strategy in patients with carotid atherosclerosis, we tested whether circulating IL-6 levels predict carotid plaque severity, vulnerability, and progression in the Cardiovascular Health Study.

Methods

Carotid ultrasound was performed at baseline and 5 years. Plaque severity was scored 0 to 5 based on NASCET grade of stenosis. Plaque vulnerability at baseline was the presence of irregular, ulcerated or echolucent plaques. Plaque progression at 5 years was a ≥1 point increase in stenosis severity. Relationship of plasma IL-6 levels with plaque characteristics was modeled using multivariable linear (severity) or logistic (vulnerability and progression) regression. Risk factors of atherosclerosis were included as independent variables.

Results

In 4334 participants with complete data (58.9% women, 72.7 ± 5.1 years). There were 1267 (29.2%) participants with vulnerable plaque and 1474 (34.0%) with plaque progression. Log IL-6 predicted plaque severity (β = 0.09, p=0.04), vulnerability (OR = 1.22, 95% CI: 1.06-1.40, p=0.006) and progression (OR = 1.44, 95% CI: 1.23-1.69, p<0.001). In participants with >50% probability of progression, mean log IL-6 was 0.54 corresponding to 2.0 pg/mL. Dichotomizing IL-6 levels did not affect performance of regression models.

Conclusions

Plasma IL-6 predicts carotid plaque severity, vulnerability, and progression. The 2.0 pg/mL cut-off could help select individuals that would benefit from anti-IL-6 drugs for stroke prevention.
124 Multiple sclerosisand sociodemographic factors a review
Authors: Mitchell James , Wu Kit , Vidot Micha , Nitkunan Arani , Carr Georgina
Published: August 2022

Background

To improve equity of service provided to people with Multiple Sclerosis (MS), in line with the aspirations of public policy across the UK, it is imperative to understand how sociodemographic factors affect management and care of people with MS.

Methods

We conducted a focused review of literature published between 2000-2021 to outline the evidence describing the relationship between the nine protected characteristics of the Equality Act 2010 and the epidemiology, diagnosis, management, and outcomes of MS. Other factors such as deprivation, settlement status, education and employment were also explored.

Results

There is much published literature on the relationship between age, sex, geographical factors, pregnancy and MS epidemiology and management. There is also good quality evidence regarding the large disability burden caused globally. Further research is required to explore racial differences in disease onset, progression, and disability as well as the relationship between MS care and religious factors, sexual orientation, gender reassignment and socioeconomic factors, particularly in UK settings.

Discussion

Better understanding of sociodemographic factors and their relationship with MS epidemiol- ogy and management is key to improving equity of care. This review has identified gaps in knowledge that require further research.
Cardiovascular autonomic failure correlates with cutaneous autonomic denervation and patient symptoms in alpha-synucleinopathies
Authors: Koay Shiwen , Provitera Vincenzo , Vichayanrat Ekawat , Caporaso Giuseppe , Silvia Fernanda Valerio da , Santoro Lucio , Manganelli Fiore , Nolano Maria , Iodice Valeria
Published: August 2022

Introduction

Cardiovascular autonomic failure and neurogenic orthostatic hypotension (nOH) are common and disabling features of Parkinson’s disease (PD) and multiple system atrophy (MSA). Compared to PD, MSA is considered a primarily central alpha-synucleinopathy.

Aim

To characterise the relationship between cardiovascular autonomic failure and cutaneous autonomic and somatic innervation in early PD and MSA.

Methods

Fifty-five patients (37 PD, 18 MSA) within 2 years of motor onset underwent: 1) cardiovascular autonomic testing 2) plasma catecholamines 3) distal leg skin biopsies for quantification of intraepider- mal (IENF), pilomotor (PNF), and sudomotor nerve fibres (SNF), and 4) COMPASS-31 autonomic symptom questionnaires.

Results

75% with MSA and 36% with PD had OH ≥20/10mmHg. Supine noradrenaline was significantly higher in MSA vs PD with OH (264[241-304] vs 158[154-190] pg/ml, P=.03). Compared to patients without OH, patients with OH had significantly reduced cutaneous innervation (3.1[1.3-6.0] vs 7.4[5.3-8.7] IENF/mm, P=.008; 2.8[0-8.2] vs 11.8[6.5-23.4] PNF/mm, P=.007; and 0.9[0.1-1.4] vs 1.6[1.4-1.8] nm SNF/µm3,

P=.002), with no significant differences between MSA and PD with OH subgroups. Markers of cardiovas- cular autonomic failure, including severity of OH, correlated significantly with cutaneous denervation (IENF: ρ=-0.47, P=.007; PNF: ρ=-0.51, P=.004; SNF: ρ=-0.51, P=.006), and patient symptoms (COMPASS-31: ρ=0.57, P=.002).

Conclusion

Cardiovascular autonomic failure was associated with cutaneous denervation in both MSA and PD. Postganglionic denervation may contribute to the pathophysiology of cardiovascular autonomic failure and nOH, and influence response to therapeutic agents for nOH.
127 Effect of reduced blood monitoring frequency in patients on dimethyl fumarate during the COVID-19 pandemic
Authors: Vaughan David , Orazulume Obioma , Fugger Magnus , Brownlee Wallace
Published: August 2022

Background

Treatment with dimethyl fumarate (DMF) may be associated with drug-induced lymphope- nia. The Summary of Product Characteristics recommends monitoring lymphocyte counts 3-monthly, as part of a risk mitigation strategy for progressive multifocal leukoencephalopathy. In February 2020, the COVID-19 pandemic led to a reduced frequency of blood monitoring to 6-monthly in stable patients on DMF (>12 months of treatment, lymphocyte count >0.6x109).

Aim

To investigate the impact of reduced frequency of DMF blood monitoring in detection of lymphopenia.

Methods

A retrospective chart review was performed of MS patients treated with DMF since August 2015. Lymphocyte counts and demographic information was recorded. Data was analysed to determine if reduced frequency of blood monitoring led to any cases of severe lymphopenia (<0.5x109) being missed.

Results

184 DMF-treated patients were included; 120 stable patients had reduced frequency of blood monitoring during the pandemic, for a median follow-up of 15 months. Only one patient was identified a lymphocyte count <0.5 x109 during 6-monthly blood monitoring, but this was not sustained, and treatment with DMF was continued.

Conclusion

Monitoring lymphocyte counts 6-monthly does not significantly increase the risk of missing severe lymphopenia in patients stable on treatment with DMF.
130 IgLON5-antibody disease: a case series
Authors: Yapp Nicholas , Clayton Lisa , Eriksson Sofia , Sathyamoorthy Tara , Lunn Michael , Woodhall Mark , Walters Patrick , Skelly Donal , Bogdanovic Marko , Irani Sarosh
Published: August 2022

IgLON5-antibody disease is a rare disorder first described in 2014 with features which interfaces both autoimmune and neurodegenerative pathophysiological processes. It has a strong HLA association, and the diagnosis is confirmed by the presence of antibodies which bind the extracellular domain of a neuronal cell adhesion protein, Iglon5. Post-mortem findings reveal this correlates with a tauopathy and subsequent neurodegeneration affecting the hypothalamus and tegmental brainstem. We present three cases and describe their history, disease progression, management and treatment responses. We found a remarkably consistent clinical phenotype which was characterised by REM and NREM parasomnias, bulbar dysfunction causing distinctive inspiratory noises, and mixed movement disorders. Our cases were diagnosed between 1.5-2 years from symptom onset. One patient died following treatment with IVIg, whilst two have been diagnosed within the last month and started on plasma exchange and immunotherapy. We will report their clinical follow up. IgLON5-antibody disease is often diagnosed late, it is thought after irreversible neurodegeneration has occurred and symptoms are advanced. We hope to raise awareness of the classical myriad of presenting symptoms and lead to earlier diagnosis, within which a window of opportunity may exist to instigate immunotherapy and arrest ongoing autoimmune processes.
Active elite rugby participation predicts alterations in cortical thickness
Authors: Parker Thomas , Zimmerman Karl , Laverse Etienne , Bourke Niall , Graham Neil , Hesle-Grave Amanda , Zetterberg Henrik , Kemp Simon , Morris Huw , Sharp David
Published: August 2022

Background

Rugby is a collision sport with high rates of head injury. The effect of rugby participation at the elite level on cerebral grey matter structure is unclear.

Methods

Data from 44 active professional rugby players, including 21 acquired within one week of mild traumatic brain injury, and 47 healthy controls were analysed. Whole-cortex and region of interest analyses investigating the effects of rugby participation, sub-acute mild traumatic brain injury, and biomarkers of traumatic brain injury (fractional anisotropy, plasma neurofilament light and glial fibrillary acidic protein) on cortical thickness were performed. Plasma neurofilament light and glial fibrillary acidic protein concen- trations were measured using Single molecule array technology.

Results

Whole-cortex analysis revealed evidence of lower right hemisphere precentral cortical thickness in non-injured rugby players compared to controls. In region of interest analyses, there was evidence rugby participation predicted lower cortical thickness in the inferior part of the precentral sulcus (right hemisphere). In the same region, there was evidence sub-acute mild traumatic brain injury predicted higher cortical thickness compared to non-injured players, and that plasma glial fibrillary acidic protein was positively associated with cortical thickness in players with sub-acute mild traumatic brain injury. No associations with neurofilament light concentration were found.

Conclusion

We present evidence that elite rugby participation predicts alterations in cortical thickness. Larger scale study with prolonged follow-up to understand the clinical implications of these findings is warranted.
146 MRI activity versus relapses as markers of SPMS disease activity: real world and pivotal trials
Authors: Giovannoni Gavin , Ryan Suzannah , Jones Eddie , Castro Patricia Dominguez , Bezlyak Vladimir , Piani-Meier Daniella , Heras Virginia de las , Lines Carol
Published: August 2022

Objective

To evaluate the contribution of MRI activity and relapses in defining disease activity in Secondary progressive multiple sclerosis (SPMS) patients by analysing real-world data from Adelphi real-world MS Disease Specific Programme (Adelphi-MS-DSP) and to understand whether active SPMS (aSPMS) and non-active SPMC (naSPMS) are mutually exclusive groups in EXPAND.

Methods

Adelphi-MS-DSP was a non-interventional, multinational real-world study (N=37,318). Patients were categorised into aSPMS (⩾1 new lesion on the most recent MRI and/or ⩾1 relapse in the last 12-months) and naSPMS groups. In EXPAND, disease activity was defined as relapses in the 2-years before screening and with/without ⩾1 gadolinium-enhancing (Gd+) T1 lesion at baseline. Demographics, MRI and relapse status were analysed descriptively.

Results

SPMS from the Adelphi-MS-DSP were categorised as aSPMS (n=1889) and naSPMS (n=665). Disease activity for aSPMS was based on MRI lesions (59.1%), relapses (12.6%), and both (28.3%). In EXPAND, 52.6% of patients (n/N=866/1645) who had no relapse in the 2-years prior to screening and no Gd+ T1 lesions at baseline were categorised under naSPMS; of these who were on placebo, 52.7% experienced on-study relapse and/or MRI activity.

Conclusions

In both real-world and clinical studies, MRI activity appears to be a more sensitive measure of disease activity versus relapses. Funding: Novartis Pharma AG, Basel, Switzerland.
150 The 70 UK centre multiple sclerosis service and DMT prescribing audit: practical project solutions
Authors: Rog David , Hobart Jeremy , Mathews Joela
Published: August 2022

Introduction

This audit (presented ABN2021), identified multiple problems highlighting that the UK MS community should maximise influence, efficiency and data usage. Here, we addresshow.

Aim

To present practical steps taken to improve UK MS care.

Methods

Audit results were discussed with key stakeholders. Potential projects were proposed, discussed and refined. A set of deliverable projects actionable by the UK MS community was identified.

Funding models that maximise investments were considered.Results

The projects, for which funding has been sought, are:

• Clarifying roles and responsibilities of MS team members

• Website, to facilitate communication and good practice repository

• Where’s the care? – UK MS care map development

• Recording care – MS team documentation

• Measuring outcomes – MS expectation frameworks (for Patients and teams)

• Maximising core activities – making blueteq (and prescribing databases) indispensable

• Advancing data value – improving Hospital Episode Statitics

• (HES data) For delivery, quality and routine use

• Ensuring the future – making MS an attractive career option

For delivery, a ring-fenced entity (Transforming MS 4 All) was established within an existing not-for-profit community interest company (CiC).

Conclusions

These deliverable, impactful projects should improve UK MS care. Managing finances under a CiC enables transparency, accountability and reinvestment of funding, to sustain services. Neverthe- less, much more is needed.
152 AttackMS natalizumab for the treatment of people with inflammatory demyeli- nation suggestive of multiple sclerosis
Authors: Schmierer Klaus , Redha Iman , Hammond Victoria , Baker David , Barkhof Frederik , Hooper Richard , Rashid Waqar , Singh-Curry Victoria , Hobart Jeremy , Giovannoni Gavin
Published: August 2022

Background

“Hit hard and early” describes first-line use of highly-effective disease-modifying treatment (HE-DMT) in people with multiple sclerosis (pwMS). However, even in treatment-active centres, months pass from diagnosis to HE-DMT losing potentially precious time to facilitate repair and protect CNS tissue from further damage. Diagnostic uncertainty contributes to hesitancy of using HE-DMT acutely. Natali- zumab (Tysabri®) is a rapidly acting HE-DMT with favourable short-term risk profile and fast elimination.

Aims

To establish feasibility to enrol people within 14 days of onset of demyelination; to test Tysabri over 24 weeks for safety, efficacy, and to advance mechanistic understanding.

Methods

Randomised, double-blind, placebo-controlled phase IIa trial to establish efficacy superiority over placebo at 12 weeks in facilitating remyelination CNS lesions measured using magnetisation transfer ratio. To detect 50% remyelination with 90% power at 5% significance level and 10% drop-out, n=20 par- ticipants per arm will be recruited across three UK sites.

Results

A favourable REC opinion (IRAS #1003822) has been obtained; the trial is due to start recruitment in March 2022. PPI of recently diagnosed pwMS revealed strong support of AttackMS.

Conclusions

AttackMS will be the first trial of HE-DMT in people with a first event of demyelination, in a hyper-acute setting.
Long-term assessment of efgartigimod in patients with generalised myasthenia gravis: ADAPT+ study interim results
Authors: Jacob Saiju , Howard James , Bril Vera , Peric Stojan , Bleecker Jan De , T’joen Carolin , Travers Jackalyne , Utsugisawa Kimiaki , Verschuuren Jan , Mantegazza Renato
Published: August 2022

Introduction

In ADAPT, efgartigimod, a human IgG1 antibody Fc-fragment blocking neonatal Fc receptor, resulted in clinically meaningful improvement (CMI) in myasthenia gravis (MG)-specific measures. Patients completing ADAPT were eligible to enrol in ADAPT+ (open-label, 3-year extension study).

Methods

Efgartigimod, 10 mg/kg intravenous infusion administered once-weekly for 4 weeks; subsequent cycles initiated based on predefined criteria. Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) scales were completed every cycle.

Results

From ADAPT 91% patients (151/167) entered ADAPT+. As of February 2021, 106 AChR-Ab+ and 33 AChR-Ab– had received ≥1 dose of efgartigimod (including 66 ADAPT placebo patients). Mean(SD) study duration: 363(114) days. The most common adverse events (AEs) in the efgartigimod-efgartigimod and placebo-efgartigimod arms: headache (15.1%/30.3%), nasopharyngitis (8.2%/13.6%), diarrhoea (6.8%/10.6%). Five deaths occurred, none considered efgartigimod-related by investigators. AEs were predominantly mild or moderate. CMI was observed in AChR-Ab+ patients during each cycle (up to 10 cycles), comparable to improvements at week 3, cycle 1 (mean[SE]: MG-ADL, –5.1[0.34]; QMG, –4.7[0.41]). Clinical improvements mirrored maximal reductions in total IgG and AChR-Abs across all cycles. Similar results observed in AChR-Ab– patients.

Conclusions

This suggests long-term efgartigimod was well-tolerated and efficacious, regardless of antibody status. No new safety signals were identified.
164 The role of MEG in assessment and diagnosis in mTBI
Authors: Allen Christopher , Rier Lukas , Gascoyne Lauren , Dineen Robert , DasNair Roshan , Brookes Matthew , Evangelou Nikos
Published: August 2022

Introduction

This MRC Confidence in Concept funded study (Clinical Trials reference:NCT03867513) combined magnetoencephalography (MEG) with ultrahigh field 7T MRI, to look for functional and struc- tural abnormalities in mild traumatic brain injury (mTBI).

Objectives

Can those with mTBI be differentiated from non-head injured orthopaedic trauma controls by measuring brain wave activity.

Methods

We scanned 40 participants within two weeks of an emergency department visit and they underwent resting state and task specific MEG followed by 7T MRI including structural, susceptibility, and diffusion sequences. Questionnaire assessment was completed at baseline, three, and six months.

Results

Whilst most individuals with mTBI recover a significant proportion have persistent difficulties. Using a Hidden Markov Model in the mTBI cohort, we were able to demonstrate reduced beta band connec- tivity results from a loss in the temporal coincidence of bursts of activity in spatially distinct regions. This replicates our findings in a distinct sub-acute mTBI cohort. Susceptibility weight imaging revealed only two mTBI participants with microhaemorrhages, their clinical care, markers of injury severity, and recovery did not differentiate them from others in the mTBI cohort.

Conclusions

Our results suggests that mTBI may impair the dynamic coordination of neural network activity and this requires further exploration.
165 The advanced BRAIN health clinic and study of long-term neurological outcomes in retired elite athletes
Authors: Graham Neil SN , Zimmerman Karl , Parker Thomas D , Friedland Daniel , Sylvester Richard , Sharp David J
Published: August 2022

The long-term effects of elite contact sports participation on brain health are poorly understood. This clinic aims to provide expert clinical review of retired players with neurocognitive and neuropsychiatric symptoms and, in an integrated research programme, better understand their neurological outcomes.

Former professional rugby players aged 30-55 are eligible, expanding to include footballers and control participants shortly. Assessment includes questionnaires documenting head injury exposure (Ohio State Method), substance use, affective, sleep, post-traumatic and post-concussive symptoms, quality of life and behavioural difficulties, including caregiver collateral. 3T MRI is acquired incorporating volumetric T1w, FLAIR, DTI, SWI and resting state-fMRI. Blood markers of neuronal damage and neurodegeneration are taken including neurofilament light and ptau181. Plasma/serum are stored for further research analyses. Neuropsychological performance is assessed including working memory, processing speed, executive functioning and performance validity testing. Participants undergo neurological review, receiving indi- vidual level multidisciplinary assessment and support. Assessment is repeated longitudinally after two and four years.

We will test the relationship of head injury exposure, genotype, biomarkers of injury and neurodegenera- tion, cognitive, neuropsychiatric and functional status. Sub-studies incorporating 7T MRI and tau PET are planned to further clarify disease mechanisms. The work is funded by but performed independently of the Rugby Football Union.
166 Exploring interactions between traumatic brain injury and cognitive co-morbidity: descriptive case analysis from real-world monitoring
Authors: Parkinson Megan , Curtis Francesca , Dani Mel , Fertleman Michael , Kolanko Magda , Soreq Eyal , Barnaghi Payam , Sharp David , Li Lucia ,   the UK DRI Care Research & Technology Centre
Published: August 2022

Introduction

Traumatic Brain Injury (TBI) is common, and increasing in older adults, in whom functional outcomes can be particularly poor. We studied post-TBI recovery using Minder, a remote home monitor- ing system that records sleep and activity data.

Methods

We installed Minder in recently discharged patients >60years with moderate-severe TBI. We present comparative descriptive analyses of early post-discharge recovery for two male patients, cross referencing observed data against verified activities and events. Both have similar socioeconomic back- grounds, non-neurological comorbidity burden and household set-up. One had prior cognitive impair- ment (PAT1), whilst the other did not (PAT2).

Results

We present 10 weeks of sleep and activity data. The data from PAT1 revealed extremely regular sleep-wake schedule, which remained stable. There was minimal time out of bed overnight, with corresponding bathroom activity, consistent with self-reported overnight toilet trips. Conversely, PAT2’s data revealed highly irregular and fragmented sleep patterns, despite PAT2 reporting good sleep. There were significant periods out of bed overnight with activity detected in rooms throughout the house, con- sistent with carer reports of night-time wandering. A period of increased overnight activity coincided with a sequence of falls, necessitating increases in care.

Discussion

Our data suggests important interactions between cognitive comorbidity and injury on function after TBI. Our novel approach provides valuable ‘real world’ insights into TBI recovery, particularly in those with poor insight, and could also help guide clinical care.
174 Croydon neurology audit of the site of death of patients with motor neurone disease
Authors: Kanagaratnam Meneka , Boodhoo Ajay , Jeffries-Shaw Caroline , Nitkunan Arani
Published: August 2022

Getting It Right First Time (GIRFT) Neurology recommended in September 2021 to audit the site of death of patients with motor neurone disease (MND) as an indicator for whole-life management.

This retrospective audit collected data on patients with MND admitted to Croydon University Hospital during a 2-year period from April 2018. Site of death is currently not recorded so data were obtained from the multi-disciplinary team. As per NICE guidelines, data were extracted on documentation of discussions regarding resuscitation status.

Of the 20 patients admitted, 12 died. Compared to national statistics, more patients died at home (42% locally vs 27% nationally), with fewer dying in hospital (17% vs 39% nationally) and similar proportions dying in a hospice (~15%). In 8 of the 17 non-elective admissions, patients had their resuscitation status clearly documented before or during the admission.

Patients with MND at Croydon are being managed appropriately compared to national data. Systems like Coordinate My Care enable communication between primary and secondary care settings and should be used consistently. Site of death is to be documented in Model Hospital enabling easier audit of this in the future.
181 The diagnostic crisis in mTBI – proposal of a novel neurovascular approach
Authors: Das Abhijit , Dutta Anirban , Wylie Glenn , Sekhar Alakendu
Published: August 2022

Mild traumatic brain injury (TBI) is common and associated with a spectrum of symptoms, which usually resolve within 3 months. But 5%–15% of patients are left with chronic disabling symptoms which challenge the current construct of mTBI. Increasingly mTBI has been a common subject of legal cases where neu- rologists have been ensnared.

The main reason for such legal challenges is the lack of clarity in mTBI definition and prognosis. The current mTBI construct is heavily dependent on the Mayo classification of Brain Injury Assessment, where Post-traumatic amnesia (PTA) is often taken as the principal index of severity, without attention to other relevant phenomena. Unfortunately, PTA is an unreliable indicator for the whole spectrum of brain injury and there is an urgent need for a better diagnostic construct, specifically utilizing the recent advances in TBI-pathophysiology (neurovascular cascade and cone of vulnerability).

We propose 1) evaluation for all brain injuries using multimodal imaging (MRI/fNIRS) protocol to capture the dynamic neurovascular changes seen in the entire spectrum of TBI severity. 2)Explore the relation between neuroimaging changes to the clinical symptoms occurring in various TBI stages by correlat- ing the comprehensive imaging data to the structured clinical assessments. 3) We will develop a novel clinical scoring system of injury severity across the spectrum of TBI by integrating the clinical outcome data with radiological (microvascular & macroscopic) and molecular biomarkers (Salivary RNA) for use in routine clinical practice.
COVID-19 vaccination and Guillain-Barré syndrome: analyses using the National Immunoglobulin Database
Authors: Keh Ryan YS , Scanlon Sophie , Donegan Katherine , Cavanagh Sally , Foster Mark , Skelland David , Palmer James , Machado Pedro M , Carr Aisling S , Lunn Michael P
Published: August 2022

Anti-viral vaccination has rarely been associated with Guillain-Barré syndrome(GBS). We performed a population-based study of NHS England data and a UK multicentre surveillance study to investigate the relationship between COVID-19 vaccination and GBS.

We linked GBS cases from England’s National Immunoglobulin Database(NID) with COVID-19 vaccina- tion data from December 2020–July 2021. GBS temporally associated within a 6-week risk window of any COVID-19 vaccine was identified.

We prospectively collected incident UK GBS cases January–November 2021 regardless of vaccine exposure.

The NID recorded 996 English GBS cases January–October 2021. A spike of cases above the 2016-2020 average occurred March–April 2021. 198 cases occurred within 6 weeks of first-dose COVID-19 vaccina- tion (0.618cases/100,000vaccinations: 176 ChAdOx1 nCoV-19, 21 tozinameran, 1 mRNA-1273). First-dose ChAdOx1 nCoV-19 accounted for the excess of 98-140 GBS cases with a peak 24 days post-vaccination. First-dose tozinameran and second-dose any vaccination showed no excess GBS risk. The UK multicen- tre surveillance dataset (121 patients) identified no phenotypic or demographic differences between vaccine-linked and unlinked cases.

First-dose ChAdOx1 nCoV-19 vaccination is associated with excess GBS risk 0.576 (95%CI 0.481-0.691) cases/100,000 doses. No specific features are associated with vaccination-related GBS cases. The mechanism of immunogenicity of ChAdOx1 nCoV-19- warrants further study.