bluuebunny/crossref_metadata_2025_split huggingface dataset:
150  PROVE study 506: Perampanel as adjunctive therapy or monotherapy in real- world care of epilepsy patients
Authors: Kuzniecky Ruben , Wechsler Robert T , Patten Anna , Malhotra Manoj 
Published: May 2022

BackgroundWe report an analysis of PROVE Study 506 (NCT03208660) in epilepsy patients who received perampanel (adjunctive or monotherapy) during routine care.MethodsData were from patients initiating perampanel after 01-Jan-2014 (cut-off: 15-Mar-2019). Retention rate (primary endpoint; patients remaining on perampanel at 3/6/12/18/24 months following initiation [Safety Analysis Set (SAS)]), dosing and safety were assessed. Patients received adjunctive perampanel (with concomitant anti-seizure medications [ASMs]) or perampanel monotherapy (primary=without con- comitant ASMs; secondary=conversion to monotherapy).ResultsSAS included 1676 (98.4%) patients receiving adjunctive perampanel and 47 (2.8%) receiving monotherapy. Patients receiving adjunctive perampanel and perampanel monotherapy (primary, n=33/secondary, n=14) are in each relevant group. Most patients on adjunctive perampanel received 1–3 baseline ASMs (77.6%).Overall, 816 (47.9%) patients discontinued (monotherapy, n=23 [48.9%]); most commonly due to adverse event (overall, 22.8%; monotherapy, 14.9%) and inadequate therapeutic effect (overall, 13.2%; mono- therapy, 25.5%).Retention rates (24 months) were: 47.6% (adjunctive); 31.3% (primary monotherapy); 83.3% (secondary monotherapy). Mean (standard deviation) maximum perampanel doses (mg) were: adjunctive, 6.6 (3.2); monotherapy, 7.2 (2.7). Treatment-emergent adverse events occurred in 696 (adjunctive; 41.5%) and 17 (monotherapy; 36.2%) patients; dizziness was most common.ConclusionRetention on perampanel (adjunctive/monotherapy) was favourable for ≤2 years, with similar safety between groups.FundingEisai Inc.manoj_malhotra@eisai.com
155  Long-term efficacy of adjunctive cenobamate in patients with uncontrolled focal seizures
Authors: Steinhoff Bernhard , Brodie Martin , Sanchez-Alvarez Juan , Milanov Ivan , Finlan Lee , Brandt Christian 
Published: May 2022

PurposeThe results of the double-blind (DB), placebo-controlled trial C017 demonstrated that ceno- bamate achieved highly significant rates of seizure freedom vs placebo in patients with uncontrolled FOS. Here we assess the long-term efficacy of cenobamate during the open-label extension (OLE) of the 017 study.MethodsSubjects who completed the 12-weeks DB maintenance phase were eligible to continue in an optional OLE phase. The OLE started with a 2-week blinded conversion period, where all subjects converted to cenobamate at a target dose of 300mg. 360 patients completed the maintenance phase of the DB study, 98.3% (354/360) and entered the OLE study (OLE safety population, N=355; OLE ITT population, n=354). Of these 355 patients, 265 were originally randomized to Cenobamate (CNB/CNB) and 90 were originally randomized to PBO and transitioned to CNB (PBO/CNB).ResultsAs of July 2019, 58.9% (209/355) of patients were continuing in the OLE, median exposure time 4.2 (0.01–5.7) years. Overall responder rate (≥ 50% seizure frequency reduction) was 63.8%. Yearly responder rates were 65.5% (232/354), 73.8% (206/279), 73.2% (175/239) 77.4% (171/221), 80.8% (168/208) for years1 to 5 respectively. 25.5% (53/208) of evaluable patients were seizure free (100% reduction) during the 5th year of study.ConclusionsLong-term adjunctive cenobamate in adults with FOS was effective and generally well tolerated (up to 5.7 years). Responder and seizure freedom rates were consistent with those shown during the double-blind studies.lee.finlan@arvelletx.com
156  Long-term effects of perampanel on cognition, growth/development in paediatric patients with epilepsy study 311
Authors: Ben Renfroe J , Patten Anna , Malhotra Manoj , Ngo Leock Y 
Published: May 2022

BackgroundThe long-term (≤1-year) effects of adjunctive perampanel on cognition, behaviour and growth/development were assessed in paediatric patients aged 4–<12 years with partial-onset seizures (POS) (with/without secondarily generalised seizures [SGS]) or primary generalised tonic-clonic seizures (PGTCS) during Study 311 (NCT02849626).MethodsCore Study (4-week pretreatment/23-week treatment) completers could enter the Extension (29-week maintenance/4-week follow-up). Assessments included: change from baseline at Week 52 for cognition (Aldenkamp-Baker Neuropsychological Assessment Schedule [ABNAS]), behavioural/emotional problems (Child Behaviour Checklist [CBCL]), visuomotor skills (Lafayette Grooved Pegboard Test [LGPT]) and growth/development.ResultsMean standard deviation (SD) change from baseline to Week 52 in total ABNAS score was -3.3 (16.6) (n=112). Mean (SD) change from baseline at Week 52 in CBCL total problems was -6.0 (14.0) and-1.6 (14.7) for patients aged 1.5–5 (n=17) and 6–18 years (n=102), respectively; for time to complete the LGPT, this was 5.3 (48.0) seconds for patients aged ≤8 years (n=33) and 0.4 (23.2) for patients aged >8 years (n=51). No significant impact on growth/development observed.ConclusionNo clinically significant changes were observed in cognition, behaviour or growth/devel- opment parameters following long-term (≤1 year) adjunctive perampanel in paediatric patients (aged 4–<12 years) with POS, SGS or PGTCS. Funding: Eisai Inc.manoj_malhotra@eisai.com
160  Long-term cognitive effects of perampanel in paediatric patients with epilepsy by responder status and dose
Authors: Gidal Barry , Meador Kimford J , Patten Anna , Malhotra Manoj , Ngo Leock Y 
Published: May 2022

BackgroundThe long-term (≤1-year) effects of adjunctive perampanel on cognition by responder status and modal dose were assessed in paediatric patients (aged 4–<12 years) with partial-onset seizures (with/without secondarily generalised seizures) or primary generalised tonic-clonic seizures during Study 311 (NCT02849626).MethodsCore Study (4-week pretreatment/23-week treatment) completers could enter the Extension (29-week maintenance/4-week follow-up). The Aldenkamp-Baker Neuropsychological Assessment Schedule [ABNAS] was used to assess cognition (change from baseline, Weeks 23/52) by total seizure response category (<50%/≥50%/≥75%/100% responder) and modal dose (mg/day).ResultsMean (standard deviation) change from baseline in total ABNAS for Weeks 23 and 52 by response category was: <50%, 3.7 (11.5) and -3.2 (16.8); ≥50%, -4.7 (13.8) and -3.7 (18.4); ≥75%, -2.1 (11.4) and -4.2(14.8); 100%, -1.6 (18.3) and -0.6 (20.6), respectively; and by modal dose was: <4 mg/day, -5.8 (7.3) and-2.0 (7.2); 4 mg/day, -4.8 (22.4) and -10.4 (25.6); >4–6 mg/day, 1.3 (8.3) and -1.3 (10.2); >6–8 mg/day, -0.5(10.7) and 1.9 (9.4); >8–12 mg/day, -0.1 (12.8) and -7.4 (20.2); >12–16 mg/day, 2.2 (12.4) and 1.1 (14.8), respectively.ConclusionAdjunctive perampanel had few long-term effects on cognition in paediatric patients, regard- less of responder status and modal dose.FundingEisai Inc.11m2anoj_malhotra@eisai.com
163  Long-term safety of adjunctive cenobamate in patients with uncontrolled focal seizures
Authors: Morales Irene Garcia , Brodie Martin J , Milanov Ivan , Czlonkowska Anna , Brandt Christian , lan Lee Fin- , Alvarez-Baron Elena , Steinhoff Bernhard J 
Published: May 2022

PurposeResults from two double-blind, placebo-controlled studies demonstrated that adjunctive ceno- bamate significantly reduced the frequency of seizures vs placebo. Cenobamate 200mg/day achieved seizure freedom in 28.3% vs 8.8% placebo (P<0.0003; 013 study maintenance phase) and 21.1%, 11.2% for cenobamate 400mg/d and 200mg/d, respectively, vs 1% in placebo (P<0.002; 017 maintenance phase). Cenobamate also showed a favorable safety and tolerability profile. Here, we report the combined long-term safety and tolerability outcomes from the ongoing open-label extensions (OLEs) of C013 and C017.MethodsAdults with uncontrolled FOS were enrolled in two double-blind, placebo-controlled studies. Patients completing both double-blinded phases were invited to participate in OLE studies (n=504).ResultsAs of July 2019, 58.3% of the patients who entered the OLEs, continued; at baseline, median age was 38 years, and 86.5% were taking ≥2 concomitant AEDs. Median (range) length of exposure was 237 weeks (1–407). The most frequent TEAEs (≥10%) were dizziness (33.9%), somnolence (23.6%), headache (18.7%), fatigue (14.3%), diplopia (12.9%) and upper respiratory tract infections (12.3%). Most TEAEs were mild or moderate (78%). 22% experienced SAEs of which only seizure exceeded 1% (n=11). Discontinu- ations were due to TEAE (8%), withdrawal by patient (12%), lack of efficacy (12%), other (4%). No cases of DRESS were reported.ConclusionsLong-term adjunctive cenobamate treatment (up to 94 months) is generally well tolerated. Most TEAEs were CNS-related and consistent with those shown in the two double-blind studies.lee.finlan@arvelletx.com
164  Progressive multifocal leukoencephalopathy (PML) following autologous periph- eral blood stem cell transplantation for multiple myeloma
Authors: Fernandes Peter , Bennett Karina , Storrar Neill , Johnson Peter 
Published: May 2022

A 67-year-old man presented with unilateral weakness and reduced dexterity four months after autolo- gous peripheral blood stem cell transplantation for multiple myeloma. The weakness progressed over the following months, with accompanying cognitive and sensory symptoms. Brain MRI showed numerous hyper- intense T2 lesions within the subcortical white matter of both cerebral hemispheres suggestive of demy- elination, progressing rapidly on interval imaging. His CSF tested positive for JC virus, diagnostic of PML.This diagnosis was unexpected as the patient did not appear to be significantly immunocompromised and PML is extremely rare in patients with multiple myeloma. Treatment for progressive multifocal leukoen- cephalopathy is via restoring immune function; in our patient no reversible cause of immuno-suppression was present. At the time of our patient’s diagnosis no treatments had been shown to be effective against PML in clinical trials. However, in the last year both pembrolizumab and BK virus specific T-cell therapy have demonstrated efficacy against PML in published clinical trials, offering new hope for patients.Clinicians should consider a diagnosis of PML when assessing patients with neurological symptoms and signs following treatment for multiple myeloma and in other haematological conditions, particularly as efficacious treatments can now be given if PML is diagnosed early.peter.fernandes@ed.ac.uk
Multimodal MRI demonstrates task-related cortical hyper-activation and neuro- chemical alteration in amyotrophic lateral sclerosis
Authors: Edmond Evan C , Dharmadasa Thanuja , Clarke William , Talbot Kevin , Stagg Charlotte J , Turner Martin R 
Published: May 2022

BackgroundThere is a paucity of reliable markers of disease activity and progression in ALS. Better biomarkers would also reduce clinical trial duration and cost by providing more sensitive measures of target engagement. Cortical hyperexcitability with transcranial magnetic stimulation, while promising, has not yet been clinically translatable. Multimodal correlation of cortical hyperexcitability could yield more robust composite biomarkers.MethodsThis project applies multimodal non-invasive neuroimaging (MRI, MEG) and neurophysiol- ogy (TMS) to explore cortical hyperexcitability in ALS. 11 affected ALS patients, 9 age matched healthy controls and 13 asymptomatic relatives at-risk of inheriting the disease-causing C9orf72 hexanucleotide repeat expansion were studied. MRI findings are reported here (diffusion-tensor imaging [DTI], functional MRI and MR spectroscopy).ResultsRight cortical activation with contralateral finger movement was significantly increased in patients (p = 0.04), while right cortical de-activation with ipsilateral movement was lost (p = 0.01). N-acetyl-aspar- tate (p=0.04) and glutamate (p = 0.01) are significantly reduced in patients. At-risk relatives occupy an intermediate profile.DiscussionBilateral motor cortex hyperexcitability was found in ALS. Asymmetry in task-related activa- tion is consistent with previously reported loss of cortical inhibition in early ALS. Integration of multimodal imaging and neurophysiological data could explain variable phenotype and disease mechanisms in ALS.eedmond@gmail.com
176  Clinical research participation in neurology
Authors: Jacob Carmen , Copson Ellen , Galea Ian 
Published: May 2022

The benefits of clinical research for patients are well recognised. The Royal College of Physicians’ recent strategy document ‘Benefiting from the research effect’ highlights the role of NHS trusts in supporting research activity. Anecdotal evidence suggests that higher recruitment of patients to research studies in oncology compared to neurology is partly driven by a more pro-active approach by oncologists in dis- cussing clinical research participation with their patients. In an ongoing evaluation across NHS neurology and oncology services in a large teaching hospital, we are gathering views from clinical staff regarding their experience, attitudes, training, and barriers in recruiting patients to clinical studies, comparing the two specialities. To gather the patient perspective, hospital attenders from the neurology research setting (specifically the multiple sclerosis Phase III trial MS-STAT2), and from the multiple sclerosis clinical service in the same hospital are being surveyed. Preliminary results suggest that in 23/40 trial neurology patients (57.5%), there was at least one occasion where additional clinical care unrelated to the study was delivered as a result of engagement with research pathway. Comparing neurology to oncology, and neurology research with service settings, will deliver objective data to inform improvements in clinical research participation in neurology.carmen.jacob@uhs.nhs.uk
189  Association of British Neurology trainees: biennial national census
Authors: Ahmad Hena , Zarkali Angeliki , Kemp Michael J , Banerjee Gargi , Rees Richard N , Shribman Samuel , Grote Helen , Ross Russell Amy L 
Published: May 2022

BackgroundThe Association of British Neurology Trainees (ABNT) conducts a biennial census of neurology trainees.This acquires data on training, education, research, out of program experiences and trainees’ future plans, which are invaluable in shaping the future workforce. This is particularly important given the introduction and implementation of Shape of Training in 2022.AimTo review trainee perspectives on neurology specialist training in 2020.MethodsOnline questionnaire, designed by the ABNT committee, sent by email to all specialist neurology trainees and associate ABN members.ResultsResults will be reviewed and compared with previous data by members of the ABNT committee. We hope to present these results to an audience of aspiring neurologists, trainees and consultant neurologists.ConclusionThe results of this census, in combination with those conducted in 2015 and 2017, will influence Shape of Training discussions and new curriculum design. We hope the information it provides will facili- tate communication and collaboration between the ABN, Specialty Advisory Committee, Joint Royal College of Physicians Training Board and other external bodies. This will inform future workforce planning and guide the transition through curriculum reforms.hena.ahmad2@nhs.net
195  Delayed transfer of care (DToC) in neuroscience across South London: an insight through patient journeys
Authors: Wu Kit , Liu Yan , King Rachel , Ellis Cathy , Nirmalananthan Niran , Weeks Rob , Isaacs Jeremy , Dilley Michael 
Published: May 2022

IntroductionPatients with complex neurological problems often require admission to a regional neuro- science centre to undergo further investigations and treatments not available in their local hospitals. A ‘delayed transfer of care’ (DToC) occurs when a patient is ready to be discharged but is still occupying a bed. Financially, this cost £104 million in London alone where 18% of all occupied beds are due to DToC [NHSE 2016].ObjectivesTo investigate causes of DToC for Neuroscience patients between regional Neuroscience units [King’s College and St George’s Hospitals (KCH and SGH respectively)] and DGHs in the South London region.MethodWe reviewed notes of 28 neurological patients admitted to KCH from surrounding DGHs between March 2018 to June 2019. Key events of the repatriation process in relation to the patient’s hospital journey were analysed.ResultsSixteen male and twelve female patients [mean age 58.5 years (29–89)] were admitted to KCH with a median length of stay of 21.5 days, of which 8.5 days were due to delays in the internal repatriation process and 3.5 days to time waiting for an available bed at their corresponding DGH.ConclusionIn addition to traditional DToC data, we found further internal delays not previously captured. Cause analysis showed this to be a bidirectional problem. Collection of further datasets, facilitated by ODN, will help to determine variation in DToC for hospitals within a network and guide solutions.kitwu@doctors.org.uk
202  Placebo-controlled intravenous nitroglycerin phenotyping of acute attacks of cluster headache
Authors: Wei Diana Y , Goadsby Peter J 
Published: May 2022

IntroductionCluster headache (CH) is characterised by attacks of excruciating unilateral headache, ipsilateral cranial autonomic symptoms (CAS) and/or agitation. Nitroglycerin (NTG) is known to induce CH. This study is the first single-blind placebo-controlled study using intravenous NTG in CH to characterise comprehensively NTG induced CH attacks.MethodsCH patients attended three study visits in total, first visit CH patients were unblinded and received intravenous NTG 0.5mcg/kg/min over 20 minutes, if successful they were asked to return for blinded visits either receiving NTG or placebo. The clinical phenotype was recorded. The study was approved by the NHS Research Ethics Committee.ResultsThirty-three patients participated, 24 completed all study visits. Nineteen episodic cluster headache (58%) and 14 chronic cluster headache (42%). NTG brought on CH attacks (n= 26, 79%), agitation (n= 24, 73%) and CAS (n= 31, 94%) in the unblinded NTG visit. NTG brought on CH attacks (n= 19, 76%), agitation (n= 20, 80%) and CAS (n= 21, 84%) in the blinded NTG visit. Only one participant had a spontaneous CH attack (4%) in the placebo visits, four participants reported unilateral CAS symptoms, and none had agitation.ConclusionWe demonstrate that intravenous NTG effectively triggers CH attacks.diana.wei@kcl.ac.uk
204  Idiopathic intracranial hypertension in Wales: population characterisation, epidemiological trends and healthcare utilisation
Authors: Miah Latif , Strafford Huw , Fonferko-Shadrach Beata , Hollinghurst Joe , Rees Mark I , Sawhney Inder , Hadjikoutis Savvas , Powell Rob , Lacey Arron , Owen Pickrell W 
Published: May 2022

ObjectiveTo characterise the Welsh idiopathic intracranial hypertension (IIH) population, epidemiologi- cal trends and healthcare outcomes using routinely collected healthcare data.MethodsWe used primary and secondary care healthcare diagnostic codes within the Secure Anonymised Information Linkage databank to ascertain IIH cases and controls in a retrospective cohort study between 2003–2017. We validated IIH diagnosis codes using anonymised secondary care lists of IIH cases.ResultsWe analysed 35 million patient years of data (2003–2017). There were 1765 cases of IIH in 2017 (85% female). The prevalence and incidence of IIH in 2017 was 76/100,000 and 7.8/100,000, significantly increased from 2003 (prevalence=12/100,000, incidence=2.3/100,000). IIH prevalence is associated with socio-economic deprivation and increasing body mass index (BMI). 9% of people with IIH had CSF shunts with less than 0.2% having bariatric surgery. Unscheduled hospital admissions were significantly higher in the IIH cohort compared to controls; and also in IIH patients with CSF shunts compared to those without.ConclusionsIIH incidence and prevalence is increasing significantly, corresponding to population increases in BMI. This has important implications for healthcare professionals and policy makers given the comor- bidities, complications and increased healthcare utilisation and economic burden associated with IIH.lotif_miah@hotmail.com
208  Long-term efficacy of erenumab in patients with chronic migraine who failed ≥3 prior prophylactic treatments
Authors: Weatherall Mark , Gantenbein Andreas , Ritter Shannon , Snellman Josefin , Klatt Jan Klatt , Mikol Daniel 
Published: May 2022

ObjectiveErenumab is a fully human monoclonal antibody. Following a 12-wk double-blind (DB), placebo- controlled chronic migraine (CM) study, a 52-wk open-label extension (OLE) study assessed long-term efficacy and safety of erenumab. We report the long-term efficacy of erenumab in a subgroup of patients in the OLE who failed ≥3 prior prophylactic treatments due to lack of efficacy and/or poor tolerability before enrolment in the parent study.MethodsDuring the 52-wk OLE patients received erenumab every 4wks. Following a protocol amendment, patients who had not reached wk28, had a dose increase to 140mg to allow them to receive the higher dose for ≥6 months; patients completing wk28 visit remained on 70mg throughout OLE. OLE treatment phase data were summarised by visit for all pts (combined treatment groups).ResultsOf 605 pts enrolled in the OLE, 226 had ≥3 prior prophylactic TFs. Mean(SD) MMD at baseline for the TF subgroup was 18.95(4.2);overall,18.11(4.5). At wk52, erenumab treatment resulted in a sustained reduction in MMD from baseline(TF,−7.94[6.5];overall,−9.29[6.6]) and 47% of pts in the ≥3 TF subgroup achieved ≥50% response.ConclusionErenumab treatment resulted in sustained efficacy in pts with ≥3 TF, a difficult-to-treat popula- tion, with greater efficacy for 140mg vs 70mg.13m6ark.weatherall1@nhs.net
209  Increased burden of headache in patients with migraine complicated by MOH: sub-group analysis BECOME study
Authors: Panesar Pritpal , Watson David , Pozo-Rosich Patricia , Lucas Christian , Gaul Charly , Ramsden Emma , Ritter Shannon , Martelletti Paolo , Snellman Josefin 
Published: May 2022

ObjectiveTo evaluate the burden of headache in patients with chronic migraine complicated by medi- cation overuse headache (CM+MO) using patient-reported outcomes (PRO) and healthcare resource utilisation (HRU) questionnaires.MethodsBECOME was a prospective, non-interventional study conducted in 2 concurrent parts over 3 months across Europe and Israel. Part 1 assessed clinical characteristics of all patients with migraine visiting headache specialist centres over 3 months. Part 2 examined burden of disease in patients with≥1 prior prophylactic treatment failure (PPTF), ≥4 monthly migraine days (MMD). We assessed quality of life (QoL) in patients in Part 2 using PRO questionnaires.ResultsOf the 2419 patients (86.9% females; mean[SD] age 43.0[11.56] years) analysed in Part 2, 571 (23.6%) reported CM+MO. Patients with CM+MO reported lower functioning (mean[SD] EQ-5D utility scores 0.67[0.24] vs 0.78[0.21]), lower health status (EQ VAS scores 59.3[20.94] vs 69.8[19.48]), higher dis- ability (mMIDAS score 35.5[21.98] vs 21.9[17.39]) and greater proportion had grade IV disability (88.1% vs 80.1%) than those without MO.ConclusionsPatients with ≥1 PPTF reported severe burden of migraine irrespective of MO, but patients with MO had lower functioning and health status, greater severity in disability, and greater use of HRU than those without MO.pritpal.panesar@novartis.com