bluuebunny/crossref_metadata_2025_split huggingface dataset:
097 Transcranial sonography in the prodromal phase of PD
Authors: Rees Richard , Simonet Cristina , Gill Aneet , Giovannoni Gavin , Lees Andrew , Bestwick Jonathan , Noyce Alastair J , Schrag Anette 
Published: August 2022

IntroductionTranscranial sonography (TCS) has been shown to be a reliable imaging biomarker in patients with Parkinson’s disease (PD). 90% of patients with PD have enlarged nigral hyperechogenicity (SN+) compared to 10% healthy controls (HC).ObjectiveTo assess the relationship between SN+ and motor and non-motor features of prodromal PD.MethodsHigher-risk (HR) and lower-risk (LR) age- and gender-matched controls from the PREDICT-PD study were compared alongside PD patients. TCS was performed with a cut-off of 0.20cm2 for SN+. Validated scales were used to assess motor and non-motor features. All assessments were undertaken blind to risk of PD determined by the PREDICT-PD algorithm. PREDICT-PD participants were compared according to enlarged or normal SN echogenicity.Results47 PREDICT-PD participants and 13 PD patients were compared. 40/47 PREDICT-PD participants and 12/13 PD patients had good quality sonographic appearances on at least one side. 24 PREDICT-PD participants had enlarged SN+ and 23 were normal. SN+ participants had higher MDS-UPDRS III scores than those with normal SN (mean 6 vs 4, p=0.036), but did not differ in any other domain. There was no relationship between SN+ and risk of PD.ConclusionDespite evidence for use around the time of PD diagnosis in individuals with motor features of PD, we found no convincing evidence to support the use of TCS in the prodromal phase.
099 Thrombotic and haemorrhagic complications associated with PLEX, reducing the risks
Authors: Japzon Nicole , Han Ruth , Sacks Benjamin , Levee Viva , Rosser Sinead , Samaroo Yasmine , Westwood John Paul , Zambreanu Laura , Lunn Michael P , Spillane Jennifer 
Published: August 2022

BackgroundPlasma Exchange (PLEX) is an increasingly used therapy for various immune-mediated neu- rological diseases. Treatment can be complicated by potentially life-threatening clots and bleeds but there is limited data available regarding these risks.Method and Intervention: A retrospective audit of the records of patients receiving PLEX in the NHNN for neurological disease from May 2019 – October 2020 was performed to identify thrombotic and haemor- rhagic complications. A multi-disciplinary PLEX working group was created to set guidelines for all aspects of the PLEX process including mode of vascular access, use of prophylactic heparin and fluid replace- ment. The service was subsequently re-audited.Results46 patients were treated with plasma exchange between May 2019 and Oct 2020. 11% developed a thrombus requiring anticoagulation. 41% developed a haemorrhage, 42% of which required intervention.Following protocol change a review of 32 patients between November 2020 to October 2021 showed that there was a reduction of 27% in the incidence of thrombus and a 17% reduction in the incidence of haemorrhage.ConclusionPLEX is integral to the treatment of disabling and potentially fatal immune-mediated neuro-logical diseases. Careful consideration of all aspects of the PLEX process, reduces risks associated with treatment and improves patient safety.
107 Short term neuropsychiatric outcomes of STN – DBS using directional vs conven- tional ring mode stimulation
Authors: Hammersley Beth , Bonello Michael , Fahad Salam , Costa Antonio Da , Mullin Jenny , Farah Jibril , Alusi Sundus 
Published: August 2022

Achieving the best outcome from STN stimulation for the treatment of Parkinson’s disease depends on ideal electrode placement and optimum stimulation settings. Motor symptoms are known to respond well to stimulation of the dorsolateral nucleus of the subthalamus and avoidance of tissue activation of the surrounding structures that may give rise to unwanted side effects including slurred speech, gait problems and neuropsychiatric symptoms. The recent development of multidirectional stimulation systems has enabled electrical current steering to activate the desired tissue areas in order to achieve effective neuromodulation.In this audit of 16 patients who underwent STN-DBS, we looked at the short-term neuropsychiatric outcomes in patients in whom current steering was deployed to achieve the best motor control to those in whom control was achieved by conventional ring mode stimulation. The patients’ symptoms were assessed at baseline and at 12 months using validated scales for anxiety, depression, apathy, and impulsivity. There was no statistical difference in the neuro-psychiatric outcomes between the two groups. However, the number of patients in this study was small and larger studies for longer periods are required to evaluate the potential benefit of this new development in minimising the neuropsychiatric complications of this treatment.
111 Factors that affect care needs in people with Parkinson’s disease: a patient perspective
Authors: Fearn Sarah , Viana Clara Mencio , Bartolomeu-Pires Sandra , Kipps Christopher 
Published: August 2022

BackgroundThe care that people with Parkinson’s (PwP) require varies over the course of the disease. A patient perspective on the factors determining care needs over time has been lacking.Aim1) To identify the relative importance of factors that affect care needs of PwP from a patient per- spective. 2) To identify whether the relative importance of different factors varies by demographic and clinical characteristics.Method: 392 PwP completed a 5-point Likert scale to score the importance of 6 different factors that affect care needs. Means scores were obtained and factors were compared by participant age, gender, living alone, disease progression, and presence of co-morbidities.ResultsFrom a patient perspective, mobility was the most important factor for assessing care needs, followed by dexterity, eating and drinking, communication, cognitive function, and mental health. This ranking was constant across demographic and clinical characteristics. However, younger patients, females, those living alone, more progressed patients, and those with co-morbidities tended to produce higher mean scores of importance suggesting a larger impact at an individual level.ConclusionThis study determined which factors patients consider to most affect the care they require, enabling healthcare professionals to provide more personalised care to PwP.
114 Pain and objectively measured cognitive performance in adults with multiple sclerosis: a systematic review
Authors: Brown Fraser , Glasmacher Stella , Taylor Daniel , Jenkins Ruth , Chandran Siddharthan , Gillespie David , Foley Peter 
Published: August 2022

BackgroundPain and cognition are important symptoms in multiple sclerosis (MS). Cognitive processes contributing to pain experience are increasingly documented. Any relationship between pain and objectively measured cognitive performance (OMCP) in MS, including potential mediating factors such as fatigue and medication, remains unclear. Understanding this relationship may facilitate targeted treatment strategies.ObjectiveDetermine the relationship between pain and OMCP in MS.MethodsWe conducted a systematic review, following a pre-registered protocol, of clinical studies examining relationships between pain and OMCP in MS. We searched MEDLINE, Embase and PsychInfo. We assessed confounders and described findings using neuropsychologist-assigned cognitive domains. Risk of bias was assessed using a modified Newcastle-Ottawa Scale.Results10 studies were included. Eight studies identified a relationship between pain and OMCP. In six studies, worse pain scores were associated with worse cognition. However, no evidence was available for several cognitive domains. Studies infrequently controlled for confounders. Most studies were judged to be at risk of bias.ConclusionsWhile several studies suggest that pain in MS is related to worse objective cognitive perfor- mance, conclusions are limited by study design and limited evidence in many cognitive domains. Future studies should better establish this relationship and delineate the neurological substrate underpinning it.
121 The ADAMS project: protocol and baseline results
Authors: Jacobs Benjamin , Giovannoni Gavin , Noyce Alastair , Morris Huw , Dobson Ruth ,   et al
Published: August 2022

Genome-wide association studies (GWAS) of Multiple Sclerosis (MS) have focussed on populations of European ancestry. Studying MS genetics in other ancestries is necessary to ensure the generalisability of these findings.We report the design of a new collaborative MS genetics project – ‘ADAMS’. Individuals with MS from non-White-British ethnic backgrounds will be recruited either via a website – https://app.mantal.co.uk/ adams – or in-person at a participating site. We will collect demographic and phenotypic data using a combination of a baseline questionnaire and subsequent healthcare record linkage. We will collect DNA from up to 1000 participants using saliva kits (Oragene-600) and genotype individuals using the Illumina Global Screening Array version 3. Genotypes will be combined with large ancestrally-matched control datasets (UK Biobank and East London Genes and Health).We have recruited 91 participants within the first eight weeks of the study. Of this initial cohort, 73.9% are female, 84.5% were born in the UK, 32.4% identified as Asian or Asian British, 28.2% as Black, African, Caribbean or Black British, and the remainder identified as having mixed, other, or White backgrounds. 51% stated they were unlimited in their mobility. 84.7% of participants have relapse-onset forms of MS and 76.1% have ever had disease-modifying therapy. The median age at diagnosis is 30.5 and the median age at recruitment 36.7. Further recruitment and genetics results will follow over the next 3 years.
123 Oxidative stress responses – potential biomarkers in multiple sclerosis
Authors: Minton Thomas , Hares Kelly , Kemp Kevin , Scolding Neil , Rice Claire 
Published: August 2022

IntroductionOxidative stress is implicated in the pathophysiology of multiple sclerosis (MS). To investigate their potential as MS biomarkers, we compared plasma levels of two master regulators of antioxidant processes nuclear factor erythroid 2 related factor 2 (Nrf2) and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α), as well as downstream antioxidant enzymes superoxide dismutase 1 (SOD1) and catalase.MethodsPlasma levels of Nrf2, PGC1α and SOD1 were measured using enzyme-linked immunosorbent assay (ELISA). Plasma catalase levels were measured using a catalase activity assay. The results were analysed using a multiple regression model.ResultsPlasma PGC1α concentrations were higher in people with MS compared to controls and lower in patients with primary progressive MS than those with relapsing remitting MS. Plasma Nrf2 levels were increased in those on disease modifying therapy with Dimethyl fumarate, which was most pronounced 6 weeks post-initiation. Plasma Nrf2 levels fell in patients commencing Ocrelizumab. Plasma catalase activity was higher in patients with MS when compared to control, and higher in patients with progressive MS phenotypes. No statistically significant changes in plasma SOD1 levels were observed.ConclusionsOur findings support further investigation of the potential for plasma PGC1α, Nrf2 and catalase as disease biomarkers in MS.
135 The UK MS pregnancy register: baseline data from the first fifty enrolled patients
Authors: Iyer Priyanka , Craig Elaine , Brex Peter , Ford Helen , Hughes Stella , Middleton Rod , Murray Katy , Pearson Owen , Rog David , Dobson Ruth 
Published: August 2022

BackgroundWe present baseline data on the first 50 participants recruited to the UK MS Pregnancy Register.MethodsData collected via questionnaires from consenting participants until 20th December 2021 were included.Results50 participants (all with relapsing remitting MS; mean age at diagnosis 28.0 years; mean age at recruitment 33.0 years) were included. Median EDSS was 2.5 (n=16). Gestation at recruitment ranged from 2 to 40 weeks. 78% had discussed their pregnancy in advance with their MS team. 90% of patients had ever taken DMT. Of the patients that stopped DMT (n=23), 16 reported stopping for pregnancy-related reasons. Of these, 39% stopped before pregnancy and 30% following conception. 15 women are continuing DMT during their current pregnancy, taking the following DMT: Glatiramer acetate (n=5), natalizumab (n=7), Peginterferon beta-1a (n=2), not recorded (n=1). In those with prior pregnancies, 61% (14/23) reported pregnancy loss with 1 case of a rare genetic condition in the baby. None of the prior pregnancy losses happened whilst on DMT. One participant reported previous PPH and foetal macrosomia and another reported previous pre-eclampsia.ConclusionsThese results show that a patient-facing pregnancy MS registry is feasible and can collect previous adverse pregnancy outcomes. Future results will inform clinicians and women about the safety of DMT and adjunctive medication during pregnancy and postpartum.
137 Impact of absolute lymphocyte count (ALC) frequency on detection of dimethyl fumarate–associated lymphopenia
Authors: Brownlee Wallace , Hadipour-Rahimabadi Shooka , Davies Heather , Belviso Nick , Shen Changyu , Kapadia Shivani , Levin Seth , Li Hanyue 
Published: August 2022

IntroductionLymphopenia is a known adverse event of dimethyl fumarate (DMF) with treatment dis- continuation recommended for patients with severe prolonged (≥6 months) lymphopenia. Because of the COVID-19 pandemic burden on healthcare systems, we retrospectively examined the impact of absolute lymphocyte count (ALC) monitoring frequency (every-3-months vs every-6-months) on lym- phopenia detection.MethodsSamples from patients enrolled in phase 3 trials (DEFINE/CONFIRM) and the extension study (ENDORSE) were retrospectively analysed using 3-month or 6-month intervals. Lymphopenia was defined as ALC <0.91x109/L and severe lymphopenia as ALC <0.5×109/L. Times to the first lymphopenia event and first severe lymphopenia event were estimated using Kaplan-Meier methods.ResultsThe analysis included 741 patients. There were 355 lymphopenia cases (76 severe) with 3-month monitoring, and 314 cases (70 severe) with 6-month monitoring. Over 120 months, incidence of first lympho- penia event was significantly different for 3-month vs 6-month monitoring (difference range: 2.64%–6.54%; P=0.0088). Incidence of first severe lymphopenia event was not significantly different for the two intervals (P=0.5866). Proportions of patients with severe prolonged lymphopenia with 3-month and 6-month moni- toring were similar (4.0% vs 4.2%).ConclusionsThe results of this study may be informative to clinicians managing pandemic-related health- care resource burdens. Support: Biogen. Disclosures on poster.
142 Discordance between neurologists and people with MS on the presence and burden of cognitive impairment
Authors: Penner Iris Katharina , Heras Virginia de las , Jones Eddie , Castro Patricia Dominguez , Bezlyak Vladimir , Piani-Meier Daniela , Lines Carol 
Published: August 2022

IntroductionApproximately 34%-65% of people with multiple sclerosis (pwMS) develop cognitive impair- ment (CI). CI often encompasses information processing speed, memory problems, difficulty concentrat- ing, and problems using executive functions effectively. This study explores the perception of the presence of CI from the perspectives of pwMS and neurologists.MethodsUS, UK and EU retrospective data analysis from the 2011-2019 Adelphi Multiple Sclerosis Disease- Specific Programme (MS-DSP). The MS-DSP is a database where neurologists provide data on the next 10 pwMS to have a consultation, patient record form (PRF), integrated with pwMS self-reported data, patient self-completion form (PSC). Neurologists and pwMS were asked about the presence of problems concentrating.Results25,374 pwMS had a PRF. 11,220 pwMS had a PRF and PSC, of these 4294 answered the cognition section, with 62% (n=2,643) reporting CI (mild 36.8%, moderate 18.6, or extreme 6.1% problems concen- trating) in the past two weeks. For the same pwMS, neurologists reported 27% (n=1,158) currently having CI (mild 19.9%, moderate 6.8%, or severe 0.3% problems concentrating).ConclusionsA clear discordance is observed between neurologists and pwMS on their perception of the presence and severity of CI with neurologists clearly underestimating the existence. Funding: Novartis Pharma AG, Basel, Switzerland.
143 Effect of siponimod on disability progression measured by ambulation score: post hoc analysis of EXPAND
Authors: D’Souza Marcus , Giovannoni Gavin , Vermersch Patrick , Maca Jeff , Ansari Soudeh , Karlsson Goeril , Piani-Meier Daniele , Kappos Ludwig 
Published: August 2022

BackgroundIn the Phase 3 EXPAND study, siponimod reduced the Neurostatus-EDSS-measured risk of 3/6-month (M) confirmed disability progression versus placebo by 21%/26%, with more pronounced effects (31%/37%) in active SPMS (aSPMS). Here we evaluated the contribution of the Ambulation Score (AS) to measuring siponimod’s effect on disability progression.Design/MethodsThis post-hoc analysis included the overall population (OP); siponimod/placebo n=1099/546) and aSPMS/non-active (naSPMS) patients (siponimod, n=516/557; placebo, n=263/270). Outcomes included change from baseline in Neurostatus-EDSS/AS, time-to-first worsening on AS (3M/6M confirmed worsening [3M/6MCW]) by ≥1/≥2-points and categorical analysis (proportion of patients with 3M/6MCW or confirmed improvement [CI] by ≥1-point during the core study [median(range): 21(0.2–37.0) M]).ResultsIn the OP, the Neurostatus-EDSS, and more prominently, AS change from baseline, favored siponimod versus placebo at all visits (M6-M30); most pronounced at M18 (EDSS: 0.13 versus 0.23;p=0.003; AS: 0.50 versus 0.81;p=0.001). Siponimod significantly reduced the risk of 3MCW (≥1-point, HR=0.78,p=0.0046;≥2-point, 0.71,p=0.0007) and 6MCW in AS (≥1 point, 0.74, p=0.0023).In aSPMS, pronounced effects were observed in 3MCW (≥1-point, HR=0.68,p=0.002; ≥2-point, 0.60,p=0.0005); 6MCW (≥1-point, HR=0.63,p=0.0007), with fewer patients worsening/more improving on siponimod and a trend for fewer patients worsening in naSPMS.ConclusionsMore pronounced effects on the Neurostatus-EDSS and AS were observed in aSPMS. Funding: Novartis Pharma AG, Basel, Switzerland.
145 Long-term safety of ofatumumab in patients with relapsing multiple sclerosis
Authors: Hauser Stephen , Cross Anne , Winthrop Kevin , Wiendl Heniz , Nicholas Jacqueline , Meuth Sven , Giacomini Paul , Saccà Francesco , Su Wendy , Kappos Ludwig 
Published: August 2022

ObjectiveTo assess the long term safety and tolerability of ofatumumab treatment in patients with relapsing multiple sclerosis (RMS)MethodsPatients completing the core ASCLEPIOS I/II, APOLITOS and APLIOS trials could enter ALITHIOS, an ongoing, open-label, extension trial. Here, we analyze the cumulative data for up to 4 years of ofa- tumumab treatment (data cutoff: 25-Sep-2021) in the overall (N=1969), continuous (ofatumumab in core+extension; N=1292) and newly-switched (teriflunomide core and ofatumumab extension; N=677) groups. Laboratory parameters including neutrophils, lymphocytes, and serum immunoglobulin (Ig) G and IgM levels will be analyzed.ResultsIn data reported from ALITHIOS (cut-off of 29-Jan-2021), representing ofatumumab treatment for up to ~3.5 years, 83.8% of patients had ≥1 AEs (exposure-adjusted incidence rate [EAIR], 148.7) and 9.7% had ≥1 serious AEs (EAIR, 4.8) with a low incidence of serious infections (2.9%; EAIR, 1.4) and malignancies (0.3%; EAIR, 0.3). Updated safety data representing continuous ofatumumab treatment for up to 4 years will be presented at the congress.ConclusionSafety findings for up to 3.5 years show ofatumumab treatment to be generally well-tol- erated with no new safety risks identified. This additional safety data will help confirm ofatumumab’s longer-term safety profile. Funding: Novartis Pharma AG, Basel, Switzerland.
156 Association of locus of control with clinical and psychosocial aspects of living with multiple sclerosis
Authors: Rothman Isaac , Tennant Alan , Mills Roger , Young Carolyn 
Published: August 2022

AimHealth Locus of control (LOC) refers to the individual’s beliefs regarding control over their life outcomes. This study aimed to determine the influence of LOC on clinical and psychosocial aspects associated with multiple sclerosis (MS).Methods5059 participants with MS completed a questionnaire pack as part of the ongoing Trajectories of Outcome in Neurological Conditions (TONiC) study. Associations between predominant LOC, measured by the Multidimensional Health Locus of Control Scale, and a range of sociodemographic and clinical variables were explored.ResultsEach LOC predominance was found to be significantly associated with all of the clinical variables and age, but not gender or educational level. When controlling for level of disability, Chance (CLOC) was associated with higher self-efficacy and quality of life than Powerful Others (PLOC), while Internal (ILOC) had no influence on the variables. A change in LOC away from ILOC was found with disease progression.ConclusionsIn MS, believing that health is controlled mainly by chance, rather than healthcare profes- sionals or one’s self, confers the most benefit with regards to quality of life. The observed shift away from internality of LOC with MS progression may not be maladaptive, but rather a protective adaptation to reduce psychological distress.
162 Use of brain imaging and EEG for prognostication in post-cardiac arrest coma
Authors: Carey Charles , Rogers Tobias , Mohanraj Rajiv 
Published: August 2022

Introduction and AimsAccurate prognostication for comatose patients following out of hospital cardiac arrests (OOHCA) remains challenging. This study aimed to evaluate the use of CT-scans and EEGs for neuro-prognostication in comatose OOHCA patients admitted to ICU in 2 major cardiac centres.MethodsRecords of 71 patients admitted to ICU following OOHCA in 2019 were reviewed. Use of CT-scans and EEGs were compared with the European Resuscitation Council (ERC) guidelines.Results46 (64.8%) patients had withdrawal of life support (WLS) during admission. 60 (84.5%) patients had reported CT-brains, of which 26.7% showed either generalised oedema or a loss of grey-white matter distinction and 73.3% showed other ischaemic changes or normal results. 100% of patients with general- ised oedema or a loss of distinction and 59.1% patients with other ischaemic changes or normal scans had WLS during admission. EEGs were performed in 21 patients (29.6%), 18 (85.7%) of which had WLS. 22 (31.0%) patients had WLS within 72 hours of arrest. 90.9% of these patients had CT-heads and 0% had EEGs performed.ConclusionEEGs were used infrequently for neuro-prognostication and cerebral oedema and a loss of grey-white matter distinction were more often associated with WLS.