bluuebunny/crossref_metadata_2025_split huggingface dataset:
045 Delayed-release dimethyl fumarate demonstrated no difference in clinical outcomes versus fingolimod in patients with relapsing-remitting multiple sclerosis: results from the real-world effect study
Authors: Sloane Jacob , Theodore Phillips J , Calkwood Jonathan , Walt Anneke Van der , Min Jinny , Okwuokenye Macaulay , Taylor Catherine 
Published: May 2018

IntroductionIn real world comparative effectiveness studies of relapsing-remitting multiple sclerosis (RRMS) patients, treatment with delayed-release dimethyl fumarate (DMF) compared with fingolimod (FTY) for ≤2 years was associated with no statistically significant differences in relapse outcomes. We assessed the real-world effectiveness of DMF compared with FTY in RRMS patients at 12 months.MethodsEFFECT (NCT02776072) was an observational, international, retrospective, single time point, medical record review study undertaken to evaluate the effectiveness of DMF and other disease-modifying therapies (DMTs). Patient eligibility criteria included age ≥18 years, diagnosis of RRMS, treatment naïve or 1 prior DMT (interferon or glatiramer acetate), DMT treatment initiation after ,December 2010and ≥12 months of medical record data following DMT initiation. Endpoints included Kaplan-Meier estimated proportion of patients relapsed at 12 months and annualised relapse rate (ARR). Substantive baseline covariates were used in estimating propensity score. The data were divided into 4 strata using propensity score. After assessing for balance in baseline covariates between treatment groups, Kaplan-Meier estimates and estimate of treatment effects were pooled across strata of propensity score.ResultsOf the 826 DMF and 785 FTY patients enrolled at sites in 17 countries, 816 and 781 patients respectively, were included in the full analysis set. Treatment groups were balanced after propensity score stratification. At 12 months, 86% of DMF-treated patients and 94% of FTY-treated patients remained on therapy. In the trimmed full analysis set, the estimated proportion of DMF patients that relapsed at 12 months was 12% compared with 13% for FTY patients; hazard ratio (95% CI) 1.07 (0.78, 1.46; p=0.6926). At 12 months after treatment initiation, the adjusted ARR ratio (95% CI) was 1.09 (0.80, 1.49; p=0.5754) for patients treated with DMF compared with FTY.ConclusionOver 12 months, treatment with DMF versus FTY was associated with no statistically significant difference on relapse outcomes.
050 Latitude continues to be associated with ms prevalence: an updated meta-analysis
Authors: Wang Wendy , Simpson Steve , Taylor Bruce 
Published: May 2018

IntroductionPrevious studies have demonstrated a strong latitudinal gradient in multiple sclerosis (MS) prevalence, likely related to interplay between genetic and environmental factors, particularly vitamin D and sun exposure. Herein, we update our 2010 meta-analysis of the latitudinal gradient of MS prevalence, seeking to assess the presence and magnitude of the gradient and whether it has changed since our 2010 analysis.MethodsStudies published between 2010 and 2017 were located via EMBASE, ISI and PubMed, using standardised search terms; data was extracted from peer-reviewed studies. These studies were added to the studies collected in our previous analysis. Prevalence estimates were adjusted for study prevalence year. Where age/sex-specific data were available, prevalence values were age/sex standardised to the 2009 European population. For the 2010–2017 interval, 85 prevalence studies were found, 53 of which met inclusion criteria, yielding 108 new prevalence points. The latitudinal association with MS prevalence was assessed by meta-regression.ResultsThere was a significant positive gradient in MS prevalence with increasing latitude (6.89/100,000 per degree latitude), attenuating slightly to 5.60/100,000 on age-standardisation, these associations persisting on adjustment for diagnostic criteria used. Of note, the age-standardised gradient was significantly stronger (p=0.044) than that from our previous study.ConclusionThis updated meta-analysis confirms that MS prevalence is still strongly positively associated with increasing latitude.
055 Effect of common concomitant antiepileptic drugs during adjunctive treatment with perampanel: post hoc analysis from the open-label extension of a phase III study in patients with idiopathic generalised epilepsy
Authors: O’Brien Terence J , Bibbiani Francesco , Patten Anna , Laurenza Antonio , Williams Betsy 
Published: May 2018

IntroductionPerampanel is approved for adjunctive treatment of partial seizures, with or without secondarily generalised seizures, and primary generalised tonic-clonic (PGTC) seizures in epilepsy patients aged ≥12 years. Perampanel is also approved for monotherapy use for partial seizures in the US. This post hoc analysis assessed the effects of the most common concomitant Baseline antiepileptic drugs (AEDs) on discontinuation rates and treatment-emergent adverse event (TEAE) incidence during adjunctive treatment with perampanel in patients (aged ≥12 years) with idiopathic generalised epilepsy (IGE) and PGTC seizures in the open-label extension (OLEx) Phase of Study 332 (NCT02307578).MethodsPatients completing the double-blind study could receive perampanel (≤12 mg/day) during the OLEx (6 week blinded Conversion Period;≤136 weeks’ Maintenance). Here, we report results for perampanel >4–8 mg/day and >8–12 mg/day.ResultsMost common concomitant Baseline AEDs were valproic acid (n=55), lamotrigine (n=53), levetiracetam (n=37), topiramate (n=21) and zonisamide (n=12); patients may have received >1 of these Baseline AEDs. The most common reasons for discontinuing were adverse event(s) (AE), ‘other’ and patient choice. Lamotrigine: patient choice, n=6/34 (>4–8 mg/day); AE/‘other’, both n=3/19 (>8–12 mg/day). Levetiracetam: patient choice, n=5/27 (>4–8 mg/day); AE, n=2/10 (>8–12 mg/day). Topiramate: ‘other’, n=3/15 (>4–8 mg/day); AE/‘other’, both n=1/6 (>8–12 mg/day). Valproic acid: patient choice, n=6/38 (>4–8 mg/day); ‘other’, n=4/17 (>8–12 mg/day). Zonisamide: patient choice/‘other’, both n=2/10 (>4–8 mg/day); no discontinuations (>8–12 mg/day). Patient-reported TEAEs ranged from: 88.2% (lamotrigine) to 93.3% (topiramate) for perampanel >4–8 mg/day, and 70.6% (valproic acid) to 100.0% (topiramate and zonisamide) for perampanel >8–12 mg/day. The most common TEAE was dizziness.ConclusionIn this post hoc analysis, primary reasons for discontinuation and TEAE incidence differed between the most common Baseline AED subgroups and perampanel dose range, although TEAE types were similar. These data provide additional information on the safety of adjunctive perampanel in patients with IGE.Study supportEisai Inc.
063 Actinomyces cavernous sinus infection: a case and systematic literature review
Authors: Lubomski Michal , Dalgliesh James , Lee Kenneth , Damodaran Omprakash , McKew Genevieve , Reddel Stephen 
Published: May 2018

CaseWe report an unusual case of a 63 year old man who developed progressive right-sided exophthalmos, painful ophthalmoplegia, headaches and fevers with worsening depression over a two-month period, subsequently identified as an Actinomyces cavernous sinus (CS) infection. Preliminary diagnoses included giant cell arteritis then Tolosa-Hunt syndrome, with a transient response to steroids. Investigations showed a bland CSF and highly metabolically active brain FDG-PET suggesting lymphoma. Biopsy of the mass demonstrated gram-positive filamentous bacteria with Actinomyces-like colonies with sulphur granules. Actinomyces CS infections are rare. They often mimic non-infectious etiologies including other inflammatory and infiltrative conditions, vascular and neoplastic causes, particularly lymphoma.ConclusionClinicians should consider infective CS syndromes in fluctuating painful ophthalmoplegias with poor response to steroids. In our view, “Tolosa-Hunt” should not be used as a diagnosis but merely used as a descriptor for syndromes that resolve with corticosteroids in the absence of a more precise diagnosis.
066 Impact of long-term teriflunomide treatment on lymphocyte counts and infections in pooled temso and tower studies
Authors: Comi Giancarlo , Macdonell Richard , Benamor Myriam , Truffinet Philippe , Thangavelu Karthinathan , Mandel Matt , Freedman Mark S 
Published: May 2018

IntroductionIn TEMSO (NCT00134563) and TOWER (NCT00751881), teriflunomide was associated with early reductions in mean lymphocyte counts, which remained within the normal range. Here, we analyse long-term effects of teriflunomide on lymphocyte counts and infections in pooled TEMSO/TOWER core and extension data (TEMSO extension, NCT00803049).MethodsPooled data from core studies are reported for patients receiving placebo or teriflunomide 14 mg. In the extensions, placebo-treated patients received active treatment; results from pooled core and extension studies are reported for the teriflunomide 14 mg group. Lymphocyte counts were obtained every 2 weeks until Week 24, and every 6 weeks thereafter. Lymphopenia was identified from 2 consecutive lymphocyte counts below LLN and graded by Common Terminology Criteria for Adverse Events.ResultsIn the core studies, placebo/teriflunomide-treated patients rarely experienced Grade 1 (0.7%/2.1%) or 2 (0.5%/1.4%) lymphopenia. Infections were reported in placebo-treated (40.0%/75.0%) and teriflunomide-treated (73.3%/20.0%) patients with Grade 1 or 2 lymphopenia, respectively. No patients with Grade 1 lymphopenia and 1 placebo-treated patient with Grade 2 lymphopenia developed a serious infection. In the combined core and extension studies, teriflunomide-treated patients (n=1354) experienced few Grade 1 (3.0%) or 2 (2.4%) lymphopenias; infections were reported in 25/40 (62.5%) and 19/33 (57.6%) patients, respectively, vs 718/1281 (56.0%) patients without lymphopenia. Serious infections occurred in patients without lymphopenia (47 patients [3.7%]) and in those with Grade 1 (1 [2.5%]) or Grade 2 (3 [9.1%]) lymphopenia. No Grade 3/4 lymphopenias were recorded. Despite the overall low rate of lymphopenia, occurrence and severity of lymphopenia will also be reported in subgroups of Asian and white patients.ConclusionIn long-term TEMSO and TOWER trials, low-grade lymphopenia was uncommon, with no reports of high-grade lymphopenia. Infection rates were similar in patients with or without lymphopenia, consistent with an immunomodulatory mechanism of action of teriflunomide with limited impact on protective immunity.
068 Evaluation of the long-term treatment effect of teriflunomide on cognitive outcomes and association with brain volume change: data from temso and its extension study
Authors: Sprenger Till , Lechner-Scott Jeannette , Sormani Maria P , Wolinsky Jerry S , Wuerfel Jens , Thangavelu Karthinathan , Cavalier Steven , Mandel Matt , Kappos Ludwig 
Published: May 2018

IntroductionIn a blinded SIENA (Structural Image Evaluation using Normalisation of Atrophy) analysis of TEMSO (NCT00134563), teriflunomide significantly reduced brain volume loss (BVL) over 2 years vs placebo. Further analysis indicated a strong correlation between 2 year BVL and disability worsening, showing better disability outcomes for patients with lower rates of BVL. Here, we explore the relationship between BVL and long-term changes in cognitive function in TEMSO and its extension (NCT00803049).MethodsThe effect of teriflunomide on cognitive function was assessed by change from baseline in Paced Auditory Serial Addition Test (PASAT)−3 scores in the TEMSO core (n=1086) and extension (n=740) studies. To evaluate change in PASAT-3 scores over 5 years, the TEMSO population was categorised into groups defined by percentage brain volume change from baseline to Year 2 (assessed by SIENA).ResultsAdjusted mean changes from baseline to Week 96 in PASAT-3 raw/Z-scores were –0.265/–0.022 and 0.870/0.073 for placebo and teriflunomide 14 mg, respectively (difference vs placebo, p=0.0435 in both instances). Long-term improvements in PASAT-3 Z-scores were observed with teriflunomide 14 mg treatment: mean (SD) changes from baseline at Weeks 156 and 276 were 0.194 (0.634) and 0.200 (0.677), respectively. Mean (SD) units of change from baseline in raw PASAT-3 scores for teriflunomide 14 mg–treated patients at Weeks 156 and 276 were 2.36 (7.73) and 2.43 (8.24), respectively. In an association analysis, the group with least BVL from baseline to Year 2 demonstrated a significant improvement in PASAT-3 score with teriflunomide treatment over 5 years vs the group with most BVL.ConclusionTeriflunomide significantly improved PASAT-3 performance vs placebo over 5 years in the TEMSO core and extension studies. Slower rates of BVL over 2 years correlated with better long-term PASAT-3 improvement. This study suggests that BVL earlier in the disease course predicts longer-term cognitive function.Study supportSanofi.
069 Peginterferon beta-1a improves clinical and radiological disease outcomes in patients who are newly diagnosed with relapsing-remitting multiple sclerosis (RRMS): subgroup analysis of advance
Authors: Newsome Scott D , Arnold Douglas L , Yun Jang , Meergans Matthias , Naylor Maria L 
Published: May 2018

IntroductionThe pivotal phase 3 ADVANCE study evaluated the efficacy of subcutaneous peginterferon beta-1a 125 mcg every 2 weeks in RRMS patients, approximately 45% of whom were newly diagnosed and had no prior disease-modifying therapy (DMT) use. We evaluated peginterferon beta-1a’s effect on clinical and radiological disease activity in newly diagnosed, treatment-naive patients from ADVANCE.MethodsADVANCE was a 2 year double-blinded study. In year 1, patients were randomised to receive peginterferon beta-1a every 2 or 4 weeks or placebo. In year 2, placebo patients were re-randomised to receive peginterferon beta-1a every 2 or 4 weeks (delayed-treatment group). Here, the subgroup of patients diagnosed ≤1 year prior to enrolment who had no prior DMT use was analysed. Annualised relapse rate (ARR), time to first relapse, 24 week confirmed disability worsening (CDW), MRI endpoints, and safety were compared between the every-2-weeks group and the delayed-treatment group.ResultsOver 2 years, the adjusted ARR in newly diagnosed patients was 32.3% lower for the peginterferon beta-1a every-2-weeks group (n=231) than for the delayed-treatment group (n=229; p=0.0352). Time to first relapse was longer in the every-2-weeks group than in the delayed-treatment group (p=0.0101), and the rate of 24 week CDW was numerically lower in the every-2-weeks group than in the delayed-treatment group. At year 2, the number of new/newly-enhancing T2 lesions was lower in the every-2-weeks than in the delayed-treatment group (p<0.0001), although no difference in the number of gadolinium-enhancing lesions was observed. The safety profile in newly diagnosed patients was similar to that of the overall patient population.ConclusionNewly diagnosed, treatment-naive patients had significantly reduced disease activity when administered peginterferon beta-1a every 2 weeks compared with delayed-treatment patients. These results are generally consistent with results from the ADVANCE overall population and highlight the benefits of initiating therapy early in the RRMS disease course.Study supportBiogen
087 Cerebral fat embolism in a case of endoscopic oesophageal dilatation
Authors: Clarke Andrew , Vallat Wilson , Kleinig Timothy 
Published: May 2018

IntroductionFat Embolism Syndrome (FES) is rare, usually occurring in the setting of long bone fractures or trauma. Furthermore, isolated neurological form or pure cerebral fat embolism (CFE) is an atypical presentation. The authors are not aware of any previously documented cases of endoscopy related CFE without accompanying trauma.CaseA 61 year old male presented for an elective endoscopy with dilatation for known oesophageal ulcer with stricturing. In post-operative recovery one hour post dilatation, he was found to have left sided weakness, aphasia and right fixed lateral gaze, NIHSS score of 18. He subsequently developed generalised tonic clonic seizures with reduced sensorium requiring intubation. CT brain was normal. MRI brain the following day showed bi-hemispheric punctate scattered white matter diffusion weighted restrictions (starfield pattern) characteristic for CFE. There were no signs of respiratory distress or petechial skin rash. Cardiac monitoring and transthoracic echocardiography with bubble test were normal.ConclusionThis case highlights a rare presentation of an uncommon syndrome, in a previously unidentified patient cohort, and the most appropriate investigation required to diagnose CFE.
094 Vascular targeting of phosphatidylserine causing thrombotic occlusion in an arteriovenous malformation animal model
Authors: Stoodley Marcus , Gauden Andrew , Lee Vivienne , Subramanian Sinduja , Moutrie Vaughan , Zhao Zhenjun , McRobb Lucinda 
Published: May 2018

IntroductionOne third of brain arteriovenous malformations (AVMs) are untreatable with current methods. Previous work has identified phosphatidylserine externalised in the endothelial plasma membrane after treatment with radiosurgery as a potential target for biological pro-thrombotic therapy. We hypothesise that treatment of AVMs with Gamma knife radiosurgery (GKS) and a vascular targeting agent with a thrombotic compound will cause localised thrombosis within the AVM vessels.MethodsA rat animal model was used by performing an end-to-side anastomosis of the external jugular vein (EJV) to the common carotid artery. The model AVM was treated with radiosurgery (20 Gy) using a Leksell Gamma Knife. At 3 weeks following GKS a dose of a conjugate of annexin V and thrombin was administered intravenously. Groups injected with saline or thrombin alone were used as controls. At 4 weeks, an angiogram was performed with tissue harvested for histology.ResultsThere was angiographic evidence of AVM occlusion in 69% of conjugate-treated animals and none of the control animals (p=0.002). AVM occlusion occurred in 63% of the GKS group treated with conjugate (p=0.03), and in 75% of the sham-GKS conjugate treated group (p=0.009). Histological evidence of thrombus was present within the EJV and nidus of 62.5% of animals in the GKS with conjugate group and <25% of the control groups (p=0.026).ConclusionThis study demonstrates that targeting of PS with an annexin V-thrombin conjugate is effective in causing thrombotic occlusion in a model AVM. These results are the first of their kind and indicate that ligand vascular targeting with radiation sensitisation may become a potential future treatment in brain AVMs.
097 A rare case of recurrent transient global amnesia
Authors: Saleem Sameer , Patel Ronak , Gawarikar Yash 
Published: May 2018

IntroductionTransient global amnesia (TGA) is a clinical syndrome characterised by the sudden onset of anterograde amnesia accompanied by repetitive questioning, sometimes with a retrograde component, lasting up to 24 hours, without compromise of other neurologic functions.CaseA 71 year old male presented to the neurology clinic with history of recurrent episodes of reversible anterograde amnesia with repetitive questioning. His first two episodes were in May 2016 and clinically very typical of TGA. After that he had recurrent episodes and he noted that they were happening on a monthly basis. He had an episode on 24 March 2017 at Yangon airport as he was returning from a trip to Myanmar. He had had three episodes in February 2017 and two in March and April 2017 and one episode on 20 May 2017. Initial MRI brain showed frontotemporal atrophy suggestive of Alzheimer’s disease and there was hypo-perfusion on the nuclear medicine study. EEG did not show any epileptic activity. His partner described a typical episode where the patient lost his memory for the preceding 24 hours and he had repetitive questioning such as ”what day is it” repeatedly. During the entire episode, he was conscious and able to converse appropriately. He had another episode of amnesia on 19 August and was admitted and underwent an MRI of brain, which showed characteristic punctate abnormalities in the bilateral hippocampi on B2000 DWI.ConclusionThe estimated annual rate of recurrence of TGA is 5.8%. Diagnosis is made from typical clinical features and typical MRI DWI findings of punctate lesions in the hippocampal with a DWI resolution of B=2000, and a thin slice thickness of 2 to 3 mm. Our patient had 11 documented episodes of transient amnesia and was a diagnostic dilemma until the characteristic hippocampal abnormalities were demonstrated on MRI.
Anatomy of the deep venous system in vein of Galen malformation and its changes after endovascular treatment depicted by magnetic resonance venography
Authors: Winkler Olivia , Brinjikji Waleed , Lanfermann Heinrich , Brassel Friedhelm , Meila Dan 
Published: May 2018

Background and purposeIt is classically thought that the internal cerebral veins (ICV) do not communicate with the venous pouch of vein of Galen malformations (VGM). We report on the anatomy of the deep venous system in VGM with special emphasis on the drainage of the ICV and possible changes after endovascular treatment.Materials and methodsWe retrospectively analyzed DSA and 2D time-of-flight MR venograms of 55 children with VGM. We evaluated all pre- and post-operative images for the presence of the ICVs and determined their route of venous drainage.ResultsOf 55 children, pre-operative 2D MRV detected the ICVs in 19 cases (35%) compared with one case (2%) for pre-embolization DSA (2%) (P<0.0001). Of the cases in which the ICVs were seen preoperatively, in 15 cases (78.9%) the ICV drained directly into the VGM while in the other four cases, the ICV used alternative venous drainage routes. On post-operative MRV, the ICVs were seen in 17 cases (31%) on MRV and 10 cases (18.2%) on DSA with drainage into an adult-like vein of Galen in 13 cases (76%), respectively (P=0.08). In four cases normal ICV drainage into the vein of Galen was seen even when the venous sac was closed. In two cases there was a change in ICV drainage from the vein of Galen to the lateral mesencephalic vein.ConclusionThe communication of the ICV with the VGM is a common phenomenon. Different changes of venous drainage routes do occur after treatment and are best seen on MRV.