bluuebunny/crossref_metadata_2025_split huggingface dataset:
THUR 005 Two atypical presentations of pres?
Authors: Andrew Lowry , Joyutpal Das , Siân Price 
Published: October 2018

Posterior reversible encephalopathy syndrome (PRES) is characterised by acute neurological symptoms with vasogenic oedema typically in parieto-occipital lobes. PRES involving atypical locations is becoming increasingly recognised. Here we report two atypical cases.An 83-year-old male with ureteric carcinoma presented with confusion, headache and high blood pressure (170/80). MRI revealed symmetrical temporal lobe T2-hyperintensities with no mass-effect or restricted diffusion. He was treated for presumed viral encephalitis. CSF was negative. Seizure was treated with Levetiracetam. Three weeks later MRI showed worsening of temporal lobe T2-hyperintensities with mild mass-effect and one small area of restricted diffusion. Despite no treatment for hypertension, six weeks later MRI showed significant improvement. Gradient echo demonstrated multiple microhaemorrhages consistent with hypertension.A 69-year-old female presented with discitis, sepsis, fluctuating consciousness and high blood pressure (180/90). Patient reported hearing a song recurrently which could represent ‘musical hallucination’ associated with seizure. CSF was normal. She was treated with Levetiracetam. MRI showed symmetrical fronto-temporal lobe T2-hyperintensities with no mass-effect and small area of restricted diffusion. Although hypertension was not treated, one week later MRI improved significantly.In summary, MRI appearances improved in both with minimal intervention. The underlying aetiology may remain elusive, but could these be atypical presentations of PRES?
WED 109 Computer vision: a smartphone camera can ‘see’ bradykinesia
Authors: Stefan Williams , Hui Fang , Rami Qahwaji , Paschal O’Gorman , Parisa Patel , D Graham Christopher , Jane Alty 
Published: October 2018

The core clinical feature of Parkinson’s disease is bradykinesia. However, the most common method of clinical assessment, finger tapping, has poor inter-rater reliability, even among movement disorder specialists. Many technologies have been devised to objectively measure finger tapping, but virtually all involve specialised equipment, which may explain why none are in widespread use. One method involves patients tapping a smartphone screen, but this cannot detect tapping amplitude or decrement (key features of bradykinesia assessment).Computer vision takes static or moving images from a camera, and then applies computing algorithms to automatically extract useful information. It is widely used in commercial applications, such as facial detection and recognition of facial expression. Crucially, the only hardware required is a simple camera with a computer processor, and such items are ubiquitous, e.g. smartphones. We report a computing method, including the technique of ‘optical flow’, which uses video from a smartphone to detect the pixels of the hand and track their movement during finger tapping. It has the potential to detect and measure bradykinesia without the need for specialised equipment. We present striking videos and early results comparing computer vision measurements of finger tapping with clinical ratings for Parkinson’s patients and controls.
THUR 120 Postprandial hypotension in MSA and PD with autonomic failure
Authors: Ekawat Vichayanrat , Gordon Ingle , Merete Hagen Ellen , Christopher Mathias , Valeria Iodice 
Published: October 2018

IntroductionPostprandial hypotension is often reported in Parkinson’s disease with autonomic failure (PD+AF) and Multiple System Atrophy (MSA). However there has been no study directly comparing this feature between these two disorders. The aim of this study was to evaluate cardiovascular autonomic responses before and after standard liquid meal ingestion in PD+AF and MSA.MethodsPatients underwent a liquid meal challenge using a previously described protocol. Blood pressure (BP) and heart rate (HR) were measured at intervals. All participants remained supine for 45 min after the liquid meal ingestion. They underwent 10 min head-up tilt (HUT) to 60° before and 45 min after the meal.Results22 MSA and 11 PD+AF patients were identified. Supine post-prandial hypotension was significantly more common in PD+AF compared to MSA (73% vs 36%; p<0.05). Both groups had orthostatic hypotension during pre-meal tilt, with no significant difference in BP and HR when tilted post-meal between PD+AF and MSA (p>0.05).ConclusionDespite the similar degree of orthostatic hypotension on supine and HUT, postprandial hypotension is more commonly present in patients with PD+AF compared to MSA. The increased tendency to post-prandial hypotension even while supine reflects the nature of post-ganglionic sympathetic denervation in PD.
THUR 121 Identifying participants with parkinson’s disease in uk biobank
Authors: Kathryn Bush , Kristiina Rannikmae , Christian Schnier , Timothy Wilkinson , John Nolan , Michael Bennett , Jingjie Cheng , Cathie Sudlow ,   et al
Published: October 2018

BackgroundLinkage to routinely collected NHS data from primary, secondary care and death certificates enables identification of participants with Parkinson’s Disease (PD) within the UK Biobank cohort of 5 00 000 adults. Validation of the accuracy of this data is required prior to their use in research studies.MethodIn this validation study participants (n=125) with a code indicating PD were identified from a sample of 17 000 participants in the cohort. Diagnoses were validated by expert adjudicators, based on free text electronic medical records. Positive predictive values (PPV,% of cases identified that are true cases) were calculated.ResultsPrimary care diagnostic codes identified 93% of PD cases, with a PPV of 95%. Combined secondary care and death data identified 42% of PD cases with a PPV of 84%.Combining diagnostic and medication codes identified more participants, but did not increase the PPV.ConclusionsThis study suggests that linkage to routinely collected healthcare data is a reliable method for identifying participants with PD in the UK Biobank cohort.Primary care diagnostic codes identified the highest proportion of participants and had the highest PPV, demonstrating the value of using primary care data to identify cases of disease in large population based cohort studies.
WED 128 Care and unmet needs in late-stage parkinsonism: a qualitative study
Authors: Joy Read , Sarah Cable , Charlotte Löfqvist , Susanne Iwarsson , Gergely Bartl ,   CLaSP consortium, Anette Schrag 
Published: October 2018

AimTo explore experiences and views about care needs and service use by people with late-stage Parkinsonism.MethodTen participants at Hoehn and Yahr stage 4 or 5 were interviewed using semi-structured open ended questions and qualitative content analysis.FindingsDespite severe disability, participants expressed their desire to maintain normality of activities and interests in their lives. Many perceived that even though health care was provided by professionals they could do nothing more for them. Participants experienced having to ‘fit-in’ to service structures that did not always accommodate their complex needs. The quality of relationships with health care professionals and formal carers shaped perception of service provision and mediated adaptation. Informal support and knowledge on disease management were key factors in their perceived ability to remain in control and to enable normal functioning. There was common reluctance to discuss, and uncertainty about, future plans. For example, moving to a residential nursing home was perceived an undesirable but potentially necessary only option for future care.ConclusionAddressing these findings including greater flexibility of healthcare structures and better future planning could increase ability of patients with late-stage parkinsonism to remain at home and improve quality of life of patients in this late disease stage.
THUR 132 Neuroschistosomiasis: complication of a neglected tropical disease
Authors: Dorothy Joe , Thomas Boyle , Amit Roy , Guy Leschziner , Matthew Evans 
Published: October 2018

Neuroschistosomiasis is an under-recognised complication of one of the world’s most prevalent, yet neglected parasitic diseases, which if left untreated can result in severe disability. Although schistosomiasis is most commonly found in the tropics, neurologists in developed countries must have a low index of suspicion in the appropriate clinical setting.We describe a 17 year old previously fit and well Guinean lady presenting with subacute, progressive, symmetric lower limb hyperaesthesia and urinary retention. Neurological examination was consistent with a myeloradiculopathy. Initial tests revealed an eosinophilia and raised ESR. CSF and imaging findings supported the clinical diagnosis of myeloradiculopathy secondary to schistosomiasis. She responded well to empirical steroids and praziquantel with complete resolution of sensory and urinary symptoms over several weeks. Serology later confirmed the diagnosis.Transverse myelitis and myeloradiculopathy affecting the conus medullaris and/or cauda equina are the most common presentations associated with neuroschistosomiasis. Symptoms are principally due to an inflammatory response to the retained schistosome eggs. This case details the differential diagnosis of a subacute myeloradiculopathy and highlights the importance of a thorough travel history. In the appropriate clinical context, neuroschistosomiasis should be included in the differential diagnosis of a subacute myeloradiculopathy, enabling prompt diagnosis and optimal management.
WED 139 Gene expression regulation in CD4+ t-cell dysfunction in ms
Authors: James Hrastelj , Nicholas Bray , Nigel Williams , Neil Robertson 
Published: October 2018

BackgroundGenetic risk variants for complex disorders such as multiple sclerosis (MS) rarely encode protein. Growing evidence suggests risk variants regulate gene expression in specific disease-relevant cells by altering regulatory genetic sequences. This can be explored by correlating genotype at risk loci with expression of nearby genes (cis-regulation), with greatest sensitivity demonstrated in the most relevant cell types. Identifying genes under regulation by the MS risk variants could be a crucial step in identifying novel therapeutic targets.Aims1) Interrogate MS risk loci for cis-regulatory effects using allele-specific expression (ASE) analysis. 2) Establish a publicly available resource of genome-wide RNA-seq expression data in CSF-derived CD4 +T lymphocytes. 3) Correlate gene expression data with longitudinal clinical data to seek biomarkers of prognosis.Method and progressWe have extracted RNA from FACS-sorted CSF-derived CD4 +T lymphocytes from over 100 individuals. cDNA library preparation and sequencing for each sample is underway.Data analysisASE analysis makes use of a pre-selected transcribed SNP to differentiate maternal and paternal transcripts of each gene of interest. When an individual is heterozygous at an additional functional regulatory locus the ratio of maternal: paternal expression will deviate from 1:1. Each MS risk locus will be interrogated for this effect.
THUR 173 Longterms: 10-year experience of fingolimod in RRMS patients
Authors: Jeffrey Cohen , Nadia Tenenbaum , Alit Bhatt , Ron Pimentel , Ludwig Kappos 
Published: October 2018

ObjectivesPresent results for up to 10 years of fingolimod treatment in RRMS patients.MethodsLONGTERMS is an open-label, single-arm, extension study evaluating the long-term safety, tolerability and efficacy of fingolimod in patients who previously participated in earlier fingolimod studies. Key efficacy measures: annualised relapse rate (ARR), proportion of patients free of 6 month confirmed disability progression (6 m-CDP), annualised rate of new or newly enlarging T2 lesions (ARneT2), and annualised rate of brain atrophy (ARBA). Safety analyses: adverse events (AEs) and serious AEs (SAEs) frequencies.Results3168 patients were included in the analysis. ARR decreased with longer exposure from 0.26 (Month [M] 0–12) to 0.20 (M0–60) and 0.19 (M0–120). Most patients remained free from 6 m-CDP at M60 (79.3%) and M120 (68.1%). ARneT2 decreased from 1.31 (M0–12) to 0.90 (M0–60), and 0.71 (M0–120). Change in brain volume was stable throughout the study (−0.37 [M12], −0.33 [M60] and −0.32 [M120]). Long-term exposure did not raise new safety concerns. No increase in frequencies of AEs or SAEs per year was observed over long-term fingolimod treatment.ConclusionsLong-term follow-up confirmed the established safety profile of fingolimod. Treatment was associated with a sustained low level of disease activity as expressed by clinical and MRI outcomes.DisclaimerPreviously presented at ECTRIMS 2017
THUR 174 The magnify-ms study: mavenclad® tablets in active rms
Authors: de Stefano N , Achiron A , Barkhof F , Chan A , Derfuss T , Hodgkinson S , Leocani L , Montalban X , Prat A , Schmierer K , Sellebjerg F , Vermersch P , Wiendl H , Keller B , Roy S 
Published: October 2018

Authors Disclaimer: http://medpub-poster.merckgroup.com/ABN2018DISC_MAGNIFY.pdfBackgroundCladribine tablets (CT) improve clinical and MRI outcomes in patients with active RMS, with significant differences versus placebo after 24 weeks.ObjectiveDescribe the design of a study to assess the onset of CT’s clinical and MRI effects in patients with active RMS.MethodsMAGNIFY-MS is a 2 year prospective Phase IV trial (including approximately 100 centres in Europe). Eligible patients will receive two years treatment with CT 3.5 mg/kg cumulative dose. Frequent MRI assessments (including lesion count, lesion volume, brain volume and MTR) will be performed at screening, baseline and 1, 2, 3, 6, 12, 15, 18 and 24 months. Various T- and B-cell subtype counts and functional profiling (eg cytokine production) will be assessed. Clinical outcomes will include changes in cognition (SDMT), disability (EDSS/KFS, 9HPT, T25FW), relapses, NEDA, NEDAP and safety at timepoints up to 24 months.ResultsAim recruit 300 patients. Primary endpoint: change in the count of combined unique active lesions at end of 6 months versus baseline. Final outcomes expected in 2021.ConclusionsMAGNIFY-MS will provide important information on the effects of CT, including early MRI changes, insights into effects on a range of disability and cognition markers, and detailed characterization of immune cell reconstitution.Disclosure statementThis study was sponsored by EMD Serono, Inc., a business of Merck KGaA, Darmstadt, Germany (in the USA), and Merck Serono SA – Geneva, an affiliate of Merck KGaA Darmstadt, Germany (ROW).
THUR 177 Efficacy of alemtuzumab retreatment after 2 initial courses
Authors: Basil Sharrack , Barry Singer , Aaron Boster , Ann Bass , Regina Berkovich , Giancarlo Comi , Óscar Fernández , Jin Kim Ho , Volker Limmroth ,   al et,   on behalf of the CARE-MS II and CAMMS03409 Investigators
Published: October 2018

Efficacy of alemtuzumab retreatment (course [C] 3) after the initial 2 courses were evaluated (CARE-MS II, NCT00548405; extension, NCT00930553). Patients received alemtuzumab retreatment (12 mg/day, 3 consecutive days;≥12 months apart) as needed for relapse and/or MRI activity or another disease-modifying therapy (DMT) per investigator’s discretion. Assessments 12 months before C3 and up to 3 years after C3: annualised relapse rate (ARR); improved/stable Expanded Disability Status Scale (EDSS) score (versus core study baseline); 6 month confirmed disability improvement (CDI). Patients receiving another DMT were excluded. Analyses included patients who received C3 or more, with data censored at the time of C4 if a fourth course was received. Through Year 6, 88% of patients entering the extension remained on study, with 45% receiving ≥1 retreatment. ARR decreased from 0.85 (12 months before C3) to 0.20 (12 months after C3; rate ratio [95% CI], 0.24 [0.17–0.34]; p<0.0001), and remained low (0.27) 3 years after C3. 68% of patients maintained stable/improved EDSS 12 months after C3. The percentage with CDI increased from 4% (12 months before C3) to 14% (12 months after C3; p=0.0126). These findings demonstrate the efficacy of alemtuzumab C3 in patients with disease activity after the initial 2 courses.Study support: Sanofi and Bayer HealthCare Pharmaceuticals.
THUR 180 Patient support program for RRMS patients treated with DMF
Authors: Joana Monterroso , Janette Curlis , Leontia Gribben 
Published: October 2018

IntroductionIn the UK, the number of multiple sclerosis (MS) patients far exceeds the capacity of MS specialist nurses (MSSNs).MethodsBiogen and IQVIA developed a remote, nurse-led, script-based telephone line providing educational assistance and supporting treatment adherence among relapsing-remitting MS (RRMS) adult patients receiving delayed-release dimethyl fumarate (DMF; TECFIDERA). Following DMF initiation, 8 calls are scheduled over the first 3 months, followed by quarterly calls for the remainder of the first treatment year. The program began in March 2015; a new online treatment satisfaction survey started in July 2017.ResultsBased on summarized call data through November 2017, 941 total patients were enrolled from 136 UK hospitals, with a mean (median, range) of 6.9 (2, 1–117) patients/hospital. An average of 11.5 calls/patient were received. Across all 11 scheduled calls, the average time/call was 8.3 min. Over 33 months, cumulative DMF discontinuation among enrolled patients was 15.7%. Between July and November 2017, 31 patients on treatment for ≥1 year completed satisfaction surveys; 74% reported scores ≥4 (scale: 1 [poor] to 5 [excellent]).DiscussionThis program has been widely used and positively received across the UK by DMF-treated patients and may reduce the burden on MSSNs.SupportBiogen. Disclosures on poster.
WED 181 Switching early from oral DMT to fingolimod in RRMS patients
Authors: Tjalf Ziemssen , Diego Silva , Jennie Medin , Christian Cornelissen , Kathrin Ringwald , Stanley Cohan 
Published: October 2018

ObjectivesCompare the effect of fingolimod in RRMS patients who switched from first-line oral disease modifying therapies (oDMTs) vs patients who switched from injectable disease-modifying therapies (iDMTs) in PASSAGE and PANGAEA 2.0 studies.MethodsPatients who switched to fingolimod from dimethyl fumarate or teriflunomide (oDMT cohort; PASSAGE n=157, PANGAEA 2.0 n=72), or treatment naïve or after iDMTs (iDMT cohort; PASSAGE n=3484, PANGAEA 2.0 n=270). Annualised relapse rate (ARR) was recorded at months (M) 12 and 24.ResultsPASSAGE: Fingolimod reduced ARR at M12 to 0.30 and 0.26 (oDMT and iDMT cohort). Increasingly higher BL ARR were observed in the oDMT cohort patients who had received two or three DMTs (ARR=1.47 and 1.53).PANGAEA 2.0: Fingolimod reduced ARR at M12 in both cohorts but was higher in the oDMT than in the iDMT cohort (0.19 vs 0.10, p=0.01). The BL ARR in the oDMT cohort increased with the number of failed DMTs before the switch (two DMTs, 1.58; three DMTs, 1.86) and was reduced with fingolimod treatment at M12 (two DMTs, 0.18; three DMTs, 0.21).ConclusionsFingolimod is effective in controlling disease activity in RRMS patients switching from other oDMTs. Switching early results in better relapse control within 1 year of initiation.DisclaimerPreviously presented at ECTRIMS 2017.
WED 186 Effect of cladribine tablets on immune cells in patients with ms
Authors: Stuve Olaf , Soelberg-Sorensen Per , Giovannoni Gavin , Leist Thomas , Hyvert Yann , Damian Doris , Boschert Ursula 
Published: October 2018

BackgroundCladribine tablets 3.5 mg/kg (CT3.5) demonstrated efficacy in patients with early (ORACLE-MS) and relapsing MS (CLARITY/CLARITY-Extension).ObjectiveEvaluate B, T lymphocyte and natural killer (NK) cell profiles after CT administration in ORACLE-MS, CLARITY and CLARITY-Extension.MethodsLongitudinal evaluation of peripheral blood lymphocytes was conducted for patients receiving the CT (either part of the initial 3.5 mg/kg active treatment groups or placebo switched to active treatment). Absolute lymphocyte counts (ALC) and subtype dispositions were evaluated at baseline, and Weeks 5, 13, 24, 48.ResultsBaseline distributions of ALC and temporal profiles of CD19+ B and CD4+ and CD8+ T lymphocytes were generally consistent across studies. Rapid reductions were observed for CD19+ B cells (~75% reduction; Week 5), with nadirs at Week 13 (~80% reduction). Reconstitution of CD19+ B cells towards baseline occurred from Week 24–48. Lesser, discontinuous reductions also occurred for CD4+ and CD8+ T cells that had not fully returned to baseline by Week 48. CD16+/CD56+ NK cells were transiently reduced with CT, with recovery evident at Weeks 24 (29%) and 48 (23%).ConclusionsCT3.5 achieved early, discontinuous reduction of peripheral blood B cells, with rapid reconstitution towards baseline; a moderate, discontinuous reduction of T cells; and early, transient NK cell reductions.Disclaimerhttp://medpub-poster.merckgroup.com/ABN2018DISC_LymphBTNKCell.pdf
WED 188 Pangaea 2.0 interim results: switching to fingolimod
Authors: Christian Cornelissen , Tjalf Ziemssen , Raimar Kern 
Published: October 2018

ObjectivesPresent first interim results of PANGAEA 2.0 including effectiveness data of patients switching from other oral disease modifying therapies (oDMTs; dimethyl fumarate and teriflunomide) to fingolimod.MethodsPANGAEA 2.0 is an ongoing non-interventional study. As of January 2017 PANGAEA 2.0 included 1419 patients, 1116 were included in this analysis of which 183 switched from other oDMTs to fingolimod.ResultsSlight differences were observed in the number of relapses 12 months (M) before baseline (mean ± SD) (1.4±1.0 vs 1.6±1.0), the EDSS (2.2±1.6 vs 2.4±1.7) and the MSSS (3.5±2.5 vs 3.8±2.5). 67.4% of the patients switched from dimethyfumarate to fingolimod and 32.6% from teriflunomide. For 30.2% of the patients fingolimod was the second therapy since diagnosis. The annualized relapse rate (ARR,±95% CI) 6M after switch to fingolimod was reduced from 1.6±0.22 to 0.2±0.05 for the patients switching from other oDMTs. For all patients the ARR was reduced from 1.3±0,06 to 0,14±0,02. The EDSS (±95% CI) remained stable at 2.4±0.37 (2.5±0.50 respectively).ConclusionsThese data indicate that active disease patients switching from dimethyl fumarate or teriflunomide to fingolimod can benefit from this switch.Disclaimerpreviously presented at ECTRIMS 2017.