bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

IntroductionAnosmia 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.ObjectiveTo identify prodromal markers of PD in patients with idiopathic anosmia (IA).MethodsPatients 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.ResultsWe 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.ConclusionParticipants 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

BackgroundAtaxia-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.Methods26 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.ResultsThe 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.ConclusionsWe 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

BackgroundParkinson 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.MethodsWe 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.ResultsThe combined M/F prevalence ratio was 1.18 (95% CI 1.03-1.36) and incidence ratio was1.37 (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.ConclusionThe 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

IntroductionHuntington’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.MethodsThis 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.Results31 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 AimsInterleukin-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.MethodsCarotid 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.ResultsIn 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.ConclusionsPlasma 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

BackgroundTo 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.MethodsWe 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.ResultsThere 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.DiscussionBetter 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

IntroductionCardiovascular 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.AimTo characterise the relationship between cardiovascular autonomic failure and cutaneous autonomic and somatic innervation in early PD and MSA.MethodsFifty-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.Results75% 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).ConclusionCardiovascular 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

BackgroundTreatment 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).AimTo investigate the impact of reduced frequency of DMF blood monitoring in detection of lymphopenia.MethodsA 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.Results184 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.ConclusionMonitoring lymphocyte counts 6-monthly does not significantly increase the risk of missing severe lymphopenia in patients stable on treatment with DMF.
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

BackgroundRugby 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.MethodsData 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.ResultsWhole-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.ConclusionWe 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

ObjectiveTo 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.MethodsAdelphi-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.ResultsSPMS 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.ConclusionsIn 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

IntroductionThis audit (presented ABN2021), identified multiple problems highlighting that the UK MS community should maximise influence, efficiency and data usage. Here, we addresshow.AimTo present practical steps taken to improve UK MS care.MethodsAudit 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.ResultsThe 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 optionFor delivery, a ring-fenced entity (Transforming MS 4 All) was established within an existing not-for-profit community interest company (CiC).ConclusionsThese 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.AimsTo 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.MethodsRandomised, 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.ResultsA 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.ConclusionsAttackMS will be the first trial of HE-DMT in people with a first event of demyelination, in a hyper-acute setting.